245 research outputs found

    A High-resolution Large-eddy Simulation Framework for Wildfire Predictions using TensorFlow

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    As the impact of wildfires has become increasingly more severe over the last decades, there is continued pressure for improvements in our ability to predict wildland fire behavior over a wide range of conditions. One approach towards this goal is through coupled fire/atmosphere modeling tools. While significant progress has been made on advancing their physical fidelity, existing modeling tools have not taken full advantage of emerging programming paradigms and computing architectures to enable high-resolution wildfire simulations. By addressing this gap, this work presents a new wildfire simulation framework that enables landscape-scale wildfire simulations with physical representation of the combustion at affordable computational cost. This is achieved by developing a coupled fire/atmosphere model in the TensorFlow programming paradigm, which enables highly efficient and scalable computations on Tensor Processing Unit (TPU) hardware architecture. To validate this simulation framework and demonstrate its efficiency, simulations of the prescribed fire experiment FireFlux II (Clements et al., 2019) are performed. By considering a parametric study on the mesh resolution, we show that the global quantities such as volumetric heat release and fire-spread rate are insensitive to the horizontal mesh resolution within a range between 0.5 m and 2 m, which is sufficient for predicting fire intermittency and dynamic fire properties associated with fine-scale turbulent structures in the atmospheric boundary layer.Comment: 10 figures, 2 tables, 4559 word

    Predictors of Lost to Follow-Up among Children with Type 2 Diabetes

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    Background/Aims: Youth with type 2 diabetes (T2D) have poor compliance with medical care. This study aimed to determine which demographic and clinical factors differ between youth with T2D who receive care in a pediatric diabetes center versus youth lost to follow-up for >18 months. Methods: Data were analyzed from 496 subjects in the PeΒ­diatric Diabetes Consortium registry. Enrollment variables were selected a priori and analyzed with univariable and multivariable logistic regression models. Results: After a median of 1.3 years from enrollment, 55% of patients were lost to follow-up. The final model included age, race/ethnicity, parent education, and estimated distance to study site. The odds ratio (99% confidence interval) of loss to follow-up was 2.87 (1.34, 6.16) for those aged 15 to <18 years versus those aged 10 to <13 years and 6.57 (2.67, 16.15) for those aged β‰₯18 years versus those aged 10 to <13 years. Among patients living more than 50 miles from the clinic, the odds ra tio of loss to follow-up was 3.11 (1.14, 8.49) versus those living within 5 miles of the site. Conclusion: Older adolescents with T2D are more likely to be lost to follow-up, but other socioeconomic factors were not significant predictors of clinic follow-up

    The Shaping of T Cell Receptor Recognition by Self-Tolerance

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    SummaryDuring selection of the TΒ cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes TΒ cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the NΒ terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire

    CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence

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    The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a β€œlock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors

    A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition

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    Little is known regarding the basis for selection of the semi-invariant Ξ±Ξ² T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d–glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3Ξ² composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR Ξ±- and semi-invariant Ξ²-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved β€œhot spot” that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3Ξ² loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR–CD1d–glycolipid interaction in which the invariant CDR3Ξ± loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant Ξ±Ξ² TCR and the unique antigen specificity of NKT cells

    The likelihood of extinction of iconic and dominant herbivores and detritivores of coral reefs: the parrotfishes and surgeonfishes

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    Parrotfishes and surgeonfishes perform important functional roles in the dynamics of coral reef systems. This is a consequence of their varied feeding behaviors ranging from targeted consumption of living plant material (primarily surgeonfishes) to feeding on detrital aggregates that are either scraped from the reef surface or excavated from the deeper reef substratum (primarily parrotfishes). Increased fishing pressure and widespread habitat destruction have led to population declines for several species of these two groups. Species-specific data on global distribution, population status, life history characteristics, and major threats were compiled for each of the 179 known species of parrotfishes and surgeonfishes to determine the likelihood of extinction of each species under the Categories and Criteria of the IUCN Red List of Threatened Species. Due in part to the extensive distributions of most species and the life history traits exhibited in these two families, only three (1.7%) of the species are listed at an elevated risk of global extinction. The majority of the parrotfishes and surgeonfishes (86%) are listed as Least Concern, 10% are listed as Data Deficient and 1% are listed as Near Threatened. The risk of localized extinction, however, is higher in some areas, particularly in the Coral Triangle region. The relatively low proportion of species globally listed in threatened Categories is highly encouraging, and some conservation successes are attributed to concentrated conservation efforts. However, with the growing realization of man's profound impact on the planet, conservation actions such as improved marine reserve networks, more stringent fishing regulations, and continued monitoring of the population status at the species and community levels are imperative for the prevention of species loss in these groups of important and iconic coral reef fishes

    A Naturally Selected Dimorphism within the HLA-B44 Supertype Alters Class I Structure, Peptide Repertoire, and T Cell Recognition

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    HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the Ξ±2 helix (B*4402 Asp156β†’B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this β€œminimal” mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire

    Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

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    Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes
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