90 research outputs found

    Combination of Variable Active Site Residues Interact to Modulate Response Regulator Reaction Kinetics

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    Signal transduction pathways are responsible for sensing and responding to stimuli. Two- component systems are a common type of signaling pathway found in microorganisms and plants, and are composed of a sensor kinase (SK) and response regulator (RR) protein. Changes in the phosphorylation states of the SK and RR due to environmental stimuli provide a molecular switch to control signal output. RRs possess the catalytic activity for phosphotransfer, but it is not known how closely related RRs self-catalyze phosphorylation and dephosphorylation reactions with rate constants that span up to six orders of magnitude. Variable residues in the RR active site, named according to their position relative to a conserved aspartic acid (D+2) and threonine residue (T+1 and T+2), individually influence autophosphorylation and autodephosphorylation reaction kinetics by one to two orders of magnitude. Our hypothesis is that certain combinations of variable active site residues interact to produce much larger effects on RR reaction kinetics than the sum of their individual effects. To investigate these interactive properties, we examined existing data on the effects of specific D+2 and T+2 combinations, in the presence of the most common T+1 residue (Ala), that resulted in synergistic interactivity. To complete characterization of position T+1, the impact of Gly (the second most abundant residue) on reaction kinetics was tested. Finally, the effects of combinations at all three positions on rate constants were tested. Results show similarity in rate constants between proteins bearing Ala or Gly at T+1, while D+2/T+1/T+2 combinations Asn/Thr/Ser and Arg/Gly/Tyr displayed no interactivity and Asn/Val/Ser was antagonistic. The T+1 results are consistent with the structural similarity of Ala and Gly. To further elucidate interactive properties, combination Arg/Gly/His is currently being investigated; however, a D+2/T+1/T+2 combination displaying synergism has yet to be observed.Bachelor of Scienc

    NAISR: A 3D Neural Additive Model for Interpretable Shape Representation

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    Deep implicit functions (DIFs) have emerged as a powerful paradigm for many computer vision tasks such as 3D shape reconstruction, generation, registration, completion, editing, and understanding. However, given a set of 3D shapes with associated covariates there is at present no shape representation method which allows to precisely represent the shapes while capturing the individual dependencies on each covariate. Such a method would be of high utility to researchers to discover knowledge hidden in a population of shapes. We propose a 3D Neural Additive Model for Interpretable Shape Representation (NAISR) which describes individual shapes by deforming a shape atlas in accordance to the effect of disentangled covariates. Our approach captures shape population trends and allows for patient-specific predictions through shape transfer. NAISR is the first approach to combine the benefits of deep implicit shape representations with an atlas deforming according to specified covariates. Although our driving problem is the construction of an airway atlas, NAISR is a general approach for modeling, representing, and investigating shape populations. We evaluate NAISR with respect to shape reconstruction, shape disentanglement, shape evolution, and shape transfer for the pediatric upper airway. Our experiments demonstrate that NAISR achieves competitive shape reconstruction performance while retaining interpretability.Comment: 20 page

    Evaluation of ACCMIP Outgoing Longwave Radiation from Tropospheric Ozone Using TES Satellite Observations.

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    We use simultaneous observations of tropospheric ozone and outgoing longwave radiation (OLR) sensitivity to tropospheric ozone from the Tropospheric Emission Spectrometer (TES) to evaluate model tropospheric ozone and its effect on OLR simulated by a suite of chemistry-climate models that participated in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP). The ensemble mean of ACCMIP models show a persistent but modest tropospheric ozone low bias (5-20 ppb) in the Southern Hemisphere (SH) and modest high bias (5-10 ppb) in the Northern Hemisphere (NH) relative to TES ozone for 2005-2010. These ozone biases have a significant impact on the OLR. Using TES instantaneous radiative kernels (IRK), we show that the ACCMIP ensemble mean tropospheric ozone low bias leads up to 120mW/ sq. m OLR high bias locally but zonally compensating errors reduce the global OLR high bias to 39+/- 41mW/ sq. m relative to TES data. We show that there is a correlation (Sq. R = 0.59) between the magnitude of the ACCMIP OLR bias and the deviation of the ACCMIP preindustrial to present day (1750-2010) ozone radiative forcing (RF) from the ensemble ozone RF mean. However, this correlation is driven primarily by models whose absolute OLR bias from tropospheric ozone exceeds 100mW/ sq. m. Removing these models leads to a mean ozone radiative forcing of 394+/- 42mW/ sq. m. The mean is about the same and the standard deviation is about 30% lower than an ensemble ozone RF of 384 +/- 60mW/ sq. m derived from 14 of the 16 ACCMIP models reported in a companion ACCMIP study. These results point towards a profitable direction of combining satellite observations and chemistry-climate model simulations to reduce uncertainty in ozone radiative forcing

    Extramedullary Hematopoiesis in the Sinonasal Cavity: A Case Report and Review of the Literature

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    Approximately 1 in 600 African-Americans are homozygous for the sickle cell gene.1 This commonly inherited hematologic disorder causes sickling of red blood cells (RBCs), prompting rapid hemolysis. A common clinical manifestation of sickle cell disease (SCD) is chronic anemia. The body responds by increasing hematopoiesis. RBC production classically occurs in the bone marrow of the long bones, pelvis, spine, and sternum. With chronically elevated erythropoietin levels, organs such as the spleen and liver help augment the body’s RBC supply. These organs are areas of fetal erythropoiesis that do not typically contribute to physiologic RBC production in adults. Other, less commonly involved organs that have been documented as sites of extramedullary hematoposesis (EMH) include lymph nodes, paravertebral regions, intra-spinal canal, pre-sacral region, nasopharynx, and paranasal sinuses

    Coronal Magnetic Field Evolution from 1996 to 2012: Continuous Non-potential Simulations

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    Coupled flux transport and magneto-frictional simulations are extended to simulate the continuous magnetic-field evolution in the global solar corona for over 15 years, from the start of Solar Cycle 23 in 1996. By simplifying the dynamics, our model follows the build-up and transport of electric currents and free magnetic energy in the corona, offering an insight into the magnetic structure and topology that extrapolation-based models cannot. To enable these extended simulations, we have implemented a more efficient numerical grid, and have carefully calibrated the surface flux-transport model to reproduce the observed large-scale photospheric radial magnetic field, using emerging active regions determined from observed line-of-sight magnetograms. This calibration is described in some detail. In agreement with previous authors, we find that the standard flux-transport model is insufficient to simultaneously reproduce the observed polar fields and butterfly diagram during Cycle 23, and that additional effects must be added. For the best-fit model, we use automated techniques to detect the latitude–time profile of flux ropes and their ejections over the full solar cycle. Overall, flux ropes are more prevalent outside of active latitudes but those at active latitudes are more frequently ejected. Future possibilities for space-weather prediction with this approach are briefly assessed

    Brecciation at the grain scale within the lithologies of the Winchcombe Mighei‐like carbonaceous chondrite

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    The Mighei‐like carbonaceous (CM) chondrites have been altered to various extents by water–rock reactions on their parent asteroid(s). This aqueous processing has destroyed much of the primary mineralogy of these meteorites, and the degree of alteration is highly heterogeneous at both the macroscale and nanoscale. Many CM meteorites are also heavily brecciated juxtaposing clasts with different alteration histories. Here we present results from the fine‐grained team consortium study of the Winchcombe meteorite, a recent CM chondrite fall that is a breccia and contains eight discrete lithologies that span a range of petrologic subtypes (CM2.0–2.6) that are suspended in a cataclastic matrix. Coordinated multitechnique, multiscale analyses of this breccia reveal substantial heterogeneity in the extent of alteration, even in highly aqueously processed lithologies. Some lithologies exhibit the full range and can comprise nearly unaltered coarse‐grained primary components that are found directly alongside other coarse‐grained components that have experienced complete pseudomorphic replacement by secondary minerals. The preservation of the complete alteration sequence and pseudomorph textures showing tochilinite–cronstedtite intergrowths are replacing carbonates suggest that CMs may be initially more carbonate rich than previously thought. This heterogeneity in aqueous alteration extent is likely due to a combination of microscale variability in permeability and water/rock ratio generating local microenvironments as has been established previously. Nevertheless, some of the disequilibrium mineral assemblages observed, such as hydrous minerals juxtaposed with surviving phases that are typically more fluid susceptible, can only be reconciled by multiple generations of alteration, disruption, and reaccretion of the CM parent body at the grain scale

    The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing.

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    Microbial ecology is plagued by problems of an abstract nature. Cell sizes are so small and population sizes so large that both are virtually incomprehensible. Niches are so far from our everyday experience as to make their very definition elusive. Organisms that may be abundant and critical to our survival are little understood, seldom described and/or cultured, and sometimes yet to be even seen. One way to confront these problems is to use data of an even more abstract nature: molecular sequence data. Massive environmental nucleic acid sequencing, such as metagenomics or metatranscriptomics, promises functional analysis of microbial communities as a whole, without prior knowledge of which organisms are in the environment or exactly how they are interacting. But sequence-based ecological studies nearly always use a comparative approach, and that requires relevant reference sequences, which are an extremely limited resource when it comes to microbial eukaryotes. In practice, this means sequence databases need to be populated with enormous quantities of data for which we have some certainties about the source. Most important is the taxonomic identity of the organism from which a sequence is derived and as much functional identification of the encoded proteins as possible. In an ideal world, such information would be available as a large set of complete, well curated, and annotated genomes for all the major organisms from the environment in question. Reality substantially diverges from this ideal, but at least for bacterial molecular ecology, there is a database consisting of thousands of complete genomes from a wide range of taxa, supplemented by a phylogeny-driven approach to diversifying genomics [2]. For eukaryotes, the number of available genomes is far, far fewer, and we have relied much more heavily on random growth of sequence databases, raising the question as to whether this is fit for purpose

    The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing

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    International audienceCurrent sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans
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