157 research outputs found

    Arachidonoyl-Phospholipid Remodeling in Proliferating Murine T Cells

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    BACKGOUND: Previous studies have shown that the functional capacity of T cells may be modulated by the composition of fatty acids within, and the release of fatty acids from membrane phospholipids, particulary containing arachidonic acid (AA). The remodeling of AA within membrane phospholipids of resting and proliferating CD4(+ )and CD8(+ )T cells is examined in this study. RESULTS: Splenic T cells were cultured in the presence or absence of anti-CD3 mAb for 48 h then labeled with [(3)H]AA for 20 min. In unstimulated cells, labeled AA was preferentially incorporated into the phosphoglycerides, phosphatidylcholine (PC) followed by phosphatidylinositol (PI) and phosphatidylethanolamine (PE). During a subsequent chase in unlabeled medium unstimulated CD4(+ )and CD8(+ )T cells demonstrated a significant and highly selective transfer of free, labeled AA into the PC pool. In contrast, proliferating CD4(+ )and CD8(+ )T cells distributed labeled [(3)H]AA predominantly into PI followed by PC and PE. Following a chase in AA-free medium, a decline in the content of [(3)H]AA-PC was observed in association with a comparable increase in [(3)H]AA-PE. Subsequent studies revealed that the cold AA content of all PE species was increased in proliferating T cells compared with that in non-cycling cells, but that enrichment in AA was observed only in the ether lipid fractions. Finally, proliferating T cells preincubated with [(3)H]AA exhibited a significant loss of labeled arachidonate in the PC fraction and an equivalent gain in labeled AA in 1-alk-1'-enyl-2-arachidonoyl-PE during a chase in unlabeled medium. CONCLUSION: This apparent unidirectional transfer of AA from PC to ether-containing PE suggests the existence of a CoA-independent transacylase system in T cells and supports the hypothesis that arachidonoyl phospholipid remodeling may play a role in the regulation of cellular proliferation

    Direct comparison of Eulerian–Eulerian and Eulerian–Lagrangian simulations for particle‐laden vertical channel flow

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    Particle‐laden flows in a vertical channel were simulated using an Eulerian–Eulerian, Anisotropic Gaussian (EE‐AG) model. Two sets of cases varying the overall mass loading were done using particle sizes corresponding to either a large or small Stokes number. Primary and turbulent statistics were extracted from these results and compared with counterparts collected from Eulerian–Lagrangian (EL) simulations. The statistics collected from the small Stokes number particle cases correspond well between the two models, with the EE‐AG model replicating the transition observed using the EL model from shear‐induced turbulence to relaminarization to cluster‐induced turbulence as the mass loading increased. The EE‐AG model was able to capture the behavior of the EL simulations only at the largest particle concentrations using the large Stokes particles. This is due to the limitations involved with employing a particle‐phase Eulerian model (as opposed to a Lagrangian representation) for a spatially intermittent system that has a low particle number concentration.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155968/1/aic16230_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155968/2/aic16230.pd

    Fine-scale simulation of ammonium and nitrate over the South Coast Air Basin and San Joaquin Valley of California during CalNex-2010

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    National ambient air quality standards (NAAQS) have been set for PM_2.5 due to its association with adverse health effects. PM_2.5 design values in the South Coast Air Basin (SoCAB) and San Joaquin Valley of California exceed NAAQS levels, and NH^(+)_(4) and NO^(-)_(3) make up the largest fraction of total PM2.5 mass on polluted days. Here we evaluate fine-scale simulations of PM_(2.5) NH^(+)_(4) and NO^(-)_(3) with the Community Multiscale Air Quality model using measurements from routine networks and the California Research at the Nexus of Air Quality and Climate Change 2010 campaign. The model correctly simulates broad spatial patterns of NH^(+)_(4) and NO^(-)_(3) including the elevated concentrations in eastern SoCAB. However, areas for model improvement have been identified. NH_3 emissions from livestock and dairy facilities appear to be too low, while those related to waste disposal in western SoCAB may be too high. Analyses using measurements from flights over SoCAB suggest that problems with NH3 predictions can influence NO^(-)_(3) predictions there. Offline ISORROPIA II calculations suggest that overpredictions of NH_x in Pasadena cause excessive partitioning of total nitrate to the particle phase overnight, while underpredictions of Na^+ cause too much partitioning to the gas phase during the day. Also, the model seems to underestimate mixing during the evening boundary layer transition leading to excessive nitrate formation on some nights. Overall, the analyses demonstrate fine-scale variations in model performance within and across the air basins. Improvements in inventories and spatial allocations of NH_3 emissions and in parameterizations of sea spray emissions, evening mixing processes, and heterogeneous ClNO_2 chemistry could improve model performance

    Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

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    When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than (1.65±0.02)×109 M⊙(1.65\pm0.02) \times 10^9~{M_\odot} using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

    Ethnic and socioeconomic variation in incidence of congenital heart defects

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    Introduction: Ethnic differences in the birth prevalence of congenital heart defects (CHDs) have been reported; however, studies of the contemporary UK population are lacking. We investigated ethnic variations in incidence of serious CHDs requiring cardiac intervention before 1 year of age. Methods: All infants who had a cardiac intervention in England and Wales between 1 January 2005 and 31 December 2010 were identified in the national congenital heart disease surgical audit and matched with paediatric intensive care admission records to create linked individual child records. Agreement in reporting of ethnic group by each audit was evaluated. For infants born 1 January 2006 to 31 December 2009, we calculated incidence rate ratios (IRRs) for CHDs by ethnicity and investigated age at intervention, antenatal diagnosis and area deprivation. Results: We identified 5350 infants (2940 (55.0%) boys). Overall CHD incidence was significantly higher in Asian and Black ethnic groups compared with the White reference population (incidence rate ratios (IRR) (95% CIs): Asian 1.5 (1.4 to 1.7); Black 1.4 (1.3 to 1.6)); incidence of specific CHDs varied by ethnicity. No significant differences in age at intervention or antenatal diagnosis rates were identified but affected children from non-White ethnic groups were more likely to be living in deprived areas than White children. Conclusions: Significant ethnic variations exist in the incidence of CHDs, including for specific defects with high infant mortality. It is essential that healthcare provision mitigates ethnic disparity, including through timely identification of CHDs at screening, supporting parental choice and effective interventions. Future research should explore the factors underlying ethnic variation and impact on longer-term outcomes

    1992 Blueberry Research Progress Reports

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    The 1992 Blueberry Research Progress Reports pertain to and report on research conducted in 1991, and were prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1992 CSRS Progress Reports: 1. Investigation of Groundwater Resources 2. Sprinkler Irrigation 3. Investigation of Preprocess Changes Leading to Berry Spoilage 4. Effect of Fertilization and Irrigation on Blueberry Quality 5. Effects of Calcium Salts and Citric Acid on Quality of Canned Lowbush Blueberries 6. Pollination of Lowbush Blueberry by Native Bees 7. Application of Heat for Controlling Insects 8. Investigations of Lowbush Blueberry Fruit Bud Cold-Hardiness 9. Steam Sterilization in Lowbush Blueberry Fields 10. Heat-Tolerant Molds 11. Vacuum Sanitation for Disease Control 12. Evaluation of Infrared Burner for Weed Control 13. Evaluation and Modification of Commercial Herbicide Wipers 14. Evaluation of Remote Sensing to Estimate Plant Cover in Lowbush Blueberry Fields 15. Comparison of Three Mechanical Blueberry Harvesters vs. Hand Raking Advisory Committee Research Reports: 16. Biology and action thresholds of secondary blueberry insects 17. Control of secondary blueberry pests 18. Control of blueberry maggot 19. Effects of calcium salts and citric acid on the quality of canned lowbush blueberries 20. The effects of postharvest handling on the dietary fiber and ellagic acid content of lowbush blueberries 21. Investigation of preprocessing changes that could lead to development of simple and inexpensive method to measure preprocessing berry spoilage 22. Determination of pesticide residue levels in fresh and processed lowbush blueberries 23. Vacuum sanitation for disease control 24. Heat-tolerant molds 25. Seedling pruning study 26. Effect of time and rate of application of Clopyralid for control of Vetch in lowbush blueberries 27. Evaluation and modification of commercial herbicide wipers 28. Effect of time of application and formulation of Hexazinone (Velpar) on Blueberry and Bunchberry 29. Evaluation of postemergence applications of Tribenuron Methyl for Bunchberry control 30. Thresholds of Dogbane and Bracken Fern by mechanical and chemical control in lowbush blueberry fields 31. Evaluation of the suitability of remote sensing to evaluate plant cover in lowbush blueberry fields 32. Evalution of infrared burner for weed control 33. Effect of time of fall pruning on growth and productivity of blueberry and evaluation of infrared burner to prune blueberries 34. Effect of Boron on lowbush blueberry fruit set and yield 35. Winter injury protection by potassium 36. Multiple cropping of wild stands 37. Nitrogen-Phosphorus study 38. Phosphorus dose/response curve 39. Investigations of lowbush blueberry fruit bud cold-hardines

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Multimessenger Gravitational-wave Searches with Pulsar Timing Arrays:Application to 3C 66B Using the NANOGrav 11-year Data Set

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    When galaxies merge, the supermassive black holes in their centers may form binaries and emit low-frequency gravitational radiation in the process. In this paper, we consider the galaxy 3C 66B, which was used as the target of the first multimessenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational-wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C 66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C 66B to less than (1.65 ± 0.02) × 109 M o˙ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data over "blind"pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences
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