112 research outputs found

    Scale dependence of cirrus heterogeneity effects. Part II: MODIS NIR and SWIR channels

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    In a context of global climate change, the understanding of the radiative role of clouds is crucial. On average, ice clouds such as cirrus have a significant positive radiative effect, but under some conditions the effect may be negative. However, many uncertainties remain regarding the role of ice clouds on Earth's radiative budget and in a changing climate. Global satellite observations are particularly well suited to monitoring clouds, retrieving their characteristics and inferring their radiative impact. To retrieve ice cloud properties (optical thickness and ice crystal effective size), current operational algorithms assume that each pixel of the observed scene is plane-parallel and homogeneous, and that there is no radiative connection between neighboring pixels. Yet these retrieval assumptions are far from accurate, as real radiative transfer is 3-D. This leads to the plane-parallel and homogeneous bias (PPHB) plus the independent pixel approximation bias (IPAB), which impacts both the estimation of top-of-the-atmosphere (TOA) radiation and the retrievals. An important factor that determines the impact of these assumptions is the sensor spatial resolution. High-spatial-resolution pixels can better represent cloud variability (low PPHB), but the radiative path through the cloud can involve many pixels (high IPAB). In contrast, low-spatial-resolution pixels poorly represent the cloud variability (high PPHB), but the radiation is better contained within the pixel field of view (low IPAB). In addition, the solar and viewing geometry (as well as cloud optical properties) can modulate the magnitude of the PPHB and IPAB. In this, Part II of our study, we simulate TOA 0.86 and 2.13 ”m solar reflectances over a cirrus uncinus scene produced by the 3DCLOUD model. Then, 3-D radiative transfer simulations are performed with the 3DMCPOL code at spatial resolutions ranging from 50&thinsp;m to 10&thinsp;km, for 12 viewing geometries and nine solar geometries. It is found that, for simulated nadir observations taken at resolution higher than 2.5&thinsp;km, horizontal radiation transport (HRT) dominates biases between 3-D and 1-D reflectance calculations, but these biases are mitigated by the side illumination and shadowing effects for off-zenith solar geometries. At resolutions coarser than 2.5&thinsp;km, PPHB dominates. For off-nadir observations at resolutions higher than 2.5&thinsp;km, the effect that we call THEAB (tilted and homogeneous extinction approximation bias) due to the oblique line of sight passing through many cloud columns contributes to a large increase of the reflectances, but 3-D radiative effects such as shadowing and side illumination for oblique Sun are also important. At resolutions coarser than 2.5&thinsp;km, the PPHB is again the dominant effect. The magnitude and resolution dependence of PPHB and IPAB is very different for visible, near-infrared and shortwave infrared channels compared with the thermal infrared channels discussed in Part I of this study. The contrast of 3-D radiative effects between solar and thermal infrared channels may be a significant issue for retrieval techniques that simultaneously use radiative measurements across a wide range of solar reflectance and infrared wavelengths.</p

    Structural and functional features and significance of the physical linkage between ER and mitochondria

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    The role of mitochondria in cell metabolism and survival is controlled by calcium signals that are commonly transmitted at the close associations between mitochondria and endoplasmic reticulum (ER). However, the physical linkage of the ER–mitochondria interface and its relevance for cell function remains elusive. We show by electron tomography that ER and mitochondria are adjoined by tethers that are ∌10 nm at the smooth ER and ∌25 nm at the rough ER. Limited proteolysis separates ER from mitochondria, whereas expression of a short “synthetic linker” (<5 nm) leads to tightening of the associations. Although normal connections are necessary and sufficient for proper propagation of ER-derived calcium signals to the mitochondria, tightened connections, synthetic or naturally observed under apoptosis-inducing conditions, make mitochondria prone to Ca2+ overloading and ensuing permeability transition. These results reveal an unexpected dependence of cell function and survival on the maintenance of proper spacing between the ER and mitochondria

    New Directions in the Radiative Transfer of Cloudy Atmospheres

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    Atmospheric radiative transfer plays a central role in understanding global climate change and anthropogenic climate forcing, and in the remote sensing of surface and atmospheric properties. Because of their opacity and highly scattering nature, clouds (covering more than half the planet at any time) pose unique challenges in atmospheric radiative transfer calculations. Some widely-used assumptions regarding clouds—such as having a flat top and base, horizontal uniformity, and infinite extent—are amenable to simple one-dimensional (1-D) radiative transfer and are therefore attractive from a computational point of view. However, these assumptions are completely unrealistic and yield errors. The ever-increasing need to realistically simulate cloud radiative processes in remote sensing and energy budget applications has contributed to the recent rapid growth of the three-dimensional (3-D) radiative transfer (RT) community [e.g., Marshak and Davis, 2005]

    Helical Chirality: a Link between Local Interactions and Global Topology in DNA

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    DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

    Incidence, risk factors, and effect on allograft survival of glomerulonephritis post-transplantation in a United Kingdom population: cohort study

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    BACKGROUND: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. METHODS: This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. RESULTS: In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. CONCLUSIONS: PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist

    Effect of hemicellulose liquid phase on the enzymatic hydrolysis of autohydrolyzed Eucalyptus globulus wood

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    In this work, Eucalyptus globulus wood was pretreated under non-isothermal autohydrolysis process at 210, 220, and 230 °C, obtaining a pretreated solid with high cellulose content and a hemicellulosic liquid phase (HLP) containing mainly xylose, acetic acid, furfural, xylooligosaccharides, and phenolic compounds. The maximum concentration of xylooligosaccharides (8.97 g/L) and phenolic compounds (2.66 g/L) was obtained at 210 and 230 °C, respectively. To evaluate the effect of HLP addition on the enzymatic hydrolysis using unwashed pretreated solid as substrate, different proportions of HLP were studied. Also, in order to use the whole slurry on enzymatic hydrolysis, the supplementation of xylanases was evaluated. Glucose concentration of 107.49 g/L (corresponding to 74.65 % of conversion) was obtained using pretreated solid at 220 °C liquid/solid ratio (LSR) of 4 g/g and enzyme solid ratio (ESR) of 25 FPU/gwithout the addition of HLP. Thus, it was shown that the unwashed pretreated solids are susceptible to enzymatic hydrolysis contributing to reduce operational cost (water consumption). Additionally, the influence of the inhibitory compounds in the HLP was shown to affect the enzymatic hydrolysis. Results indicated that 82.52 g/L of glucose (59.37 % of conversion) was obtained, using 100 % of HLP at LSR of 4 g/g and ESR of 16 FPU/g at 210 °C of pretreated solid. However, a positive effect was shown on the enzymatic hydrolysis when the xylanases were added using 100 % of HLP, increasing to 35 and 27 % in the glucose production with respect to whole slurry without addition of xylanases.The authors A. Romani and F. B. Pereira thank to the Portuguese Foundation for Science and Technology (FCT, Portugal) for their fellowships (grant number, SFRH/BPD/77995/2011 and SFRH/BD/64776/2009, respectively)

    Reversible binding and rapid diffusion of proteins in complex with inositol lipids serves to coordinate free movement with spatial information

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    Polyphosphoinositol lipids convey spatial information partly by their interactions with cellular proteins within defined domains. However, these interactions are prevented when the lipids' head groups are masked by the recruitment of cytosolic effector proteins, whereas these effectors must also have sufficient mobility to maximize functional interactions. To investigate quantitatively how these conflicting functional needs are optimized, we used different fluorescence recovery after photobleaching techniques to investigate inositol lipid–effector protein kinetics in terms of the real-time dissociation from, and diffusion within, the plasma membrane. We find that the protein–lipid complexes retain a relatively rapid (∌0.1–1 ”m2/s) diffusion coefficient in the membrane, likely dominated by protein–protein interactions, but the limited time scale (seconds) of these complexes, dictated principally by lipid–protein interactions, limits their range of action to a few microns. Moreover, our data reveal that GAP1IP4BP, a protein that binds PtdIns(4,5)P2 and PtdIns(3,4,5)P3 in vitro with similar affinity, is able to “read” PtdIns(3,4,5)P3 signals in terms of an elongated residence time at the membrane

    Measurement of inositol 1,4,5-trisphosphate in living cells using an improved set of resonance energy transfer-based biosensors

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    Improved versions of inositol-1,4,5-trisphosphate (InsP3) sensors were created to follow intracellular InsP3 changes in single living cells and in cell populations. Similar to previous InsP3 sensors the new sensors are based on the ligand binding domain of the human type-I InsP3 receptor (InsP3R-LBD), but contain a mutation of either R265K or R269K to lower their InsP3 binding affinity. Tagging the InsP3R-LBD with N-terminal Cerulean and C-terminal Venus allowed measurement of Ins P3 in single-cell FRET experiments. Replacing Cerulean with a Luciferase enzyme allowed experiments in multi-cell format by measuring the change in the BRET signal upon stimulation. These sensors faithfully followed the agonist-induced increase in InsP3 concentration in HEK 293T cells expressing the Gq-coupled AT1 angiotensin receptor detecting a response to agonist concentration as low as 10 pmol/L. Compared to the wild type InsP3 sensor, the mutant sensors showed an improved off-rate, enabling a more rapid and complete return of the signal to the resting value of InsP3 after termination of M3 muscarinic receptor stimulation by atropine. For parallel measurements of intracellular InsP3 and Ca2+ levels in BRET experiments, the Cameleon D3 Ca2+ sensor was modified by replacing its CFP with luciferase. In these experiments depletion of plasma membrane PtdIns(4,5)P2 resulted in the fall of InsP3 level, followed by the decrease of the Ca2+-signal evoked by the stimulation of the AT1 receptor. In contrast, when type-III PI 4-kinases were inhibited with a high concentration of wortmannin or a more specific inhibitor, A1, the decrease of the Ca2+-signal preceded the fall of InsP3 level indicating an InsP3-, independent, direct regulation of capacitative Ca2+ influx by plasma membrane inositol lipids. Taken together, our results indicate that the improved InsP3 sensor can be used to monitor both the increase and decrease of InsP3 levels in live cells suitable for high-throughput BRET applications. © 2015, Public Library of Science. All rights reserved

    Protein/DNA interactions in complex DNA topologies: expect the unexpected

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    DNA supercoiling results in compacted DNA structures that can bring distal sites into close proximity. It also changes the local structure of the DNA, which can in turn influence the way it is recognised by drugs, other nucleic acids and proteins. Here, we discuss how DNA supercoiling and the formation of complex DNA topologies can affect the thermodynamics of DNA recognition. We then speculate on the implications for transcriptional control and the three-dimensional organisation of the genetic material, using examples from our own simulations and from the literature. We introduce and discuss the concept of coupling between the multiple length-scales associated with hierarchical nuclear structural organisation through DNA supercoiling and topology
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