| 1561. |
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| 1562. |
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| 1563. |
- Fernandes, Ricardo A., et al.
(författare)
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A cell topography-based mechanism for ligand discrimination by the T cell receptor
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:28, s. 14002-14010
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Tidskriftsartikel (refereegranskat)abstract
- The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.
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| 1564. |
- Ferreira, P. C. L., et al.
(författare)
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Plasma biomarkers identify older adults at risk of Alzheimer's disease and related dementias in a real-world population-based cohort
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:10, s. 4507-4519
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPlasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. MethodsWe measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (A beta)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. ResultsK-medoids clustering identified two distinct plasma A beta 42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with A beta 42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. DiscussionAbnormal plasma A beta 42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. HighlightsPopulation-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data.In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E epsilon 4, and greater age.Plasma amyloid beta (A beta)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups.Plasma A beta 42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group.Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.
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| 1565. |
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| 1566. |
- Frank, B, et al.
(författare)
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Death receptor 4 variants and colorectal cancer risk
- 2006
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 15:10, s. 2002-2005
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Tidskriftsartikel (refereegranskat)
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| 1567. |
- Freelon, B., et al.
(författare)
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Low energy electronic spectroscopy of an infinite-layer cuprate : A resonant inelastic X-ray scattering study of CaCuO2
- 2010
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Ingår i: Physica. C, Superconductivity. - : Elsevier BV. - 0921-4534 .- 1873-2143. ; 470:3, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of Oxygen K-edge soft X-ray absorption and emission spectroscopy that was performed on an infinite-layer insulating cuprate thin film CaCuO2 Experimentally obtained spectra arc consistent with local density approximation calculations X-ray absorption spectra show a close resemblance to spectra obtained from homologous single crystal cuprates In addition to d-d excitations. X-ray emission spectra reveal the presence of Zhang-Rice singlet states in the infinite-layer CuO2 planes The question of whether the Zhang-Rice singlet features are masked by the O 2p main-band is addressed. it is possible to quantify the position of the Zhang-Rice singlet using emission intensity profiles X-ray emission is demonstrated as a tool for understanding CuO2 planar electronic correlation in the prototypical infinite-layer The energy difference, 2 0 eV, between the oxygen main-band and the Zhang-Rice singlet band is found to match values obtained theoretically using established planar electronic correlation parameters.
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| 1568. |
- Frieler, Katja, et al.
(författare)
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Scenario setup and forcing data for impact model evaluation and impact attribution within the third round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a)
- 2024
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Ingår i: Geoscientific Model Development. - : Copernicus Publications. - 1991-959X .- 1991-9603. ; 17:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the rationale and the protocol of the first component of the third simulation round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a, http://www.isimip.org, last access: 2 November 2023) and the associated set of climate-related and direct human forcing data (CRF and DHF, respectively). The observation-based climate-related forcings for the first time include high-resolution observational climate forcings derived by orographic downscaling, monthly to hourly coastal water levels, and wind fields associated with historical tropical cyclones. The DHFs include land use patterns, population densities, information about water and agricultural management, and fishing intensities. The ISIMIP3a impact model simulations driven by these observation-based climate-related and direct human forcings are designed to test to what degree the impact models can explain observed changes in natural and human systems. In a second set of ISIMIP3a experiments the participating impact models are forced by the same DHFs but a counterfactual set of atmospheric forcings and coastal water levels where observed trends have been removed. These experiments are designed to allow for the attribution of observed changes in natural, human, and managed systems to climate change, rising CH4 and CO2 concentrations, and sea level rise according to the definition of the Working Group II contribution to the IPCC AR6.
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| 1569. |
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| 1570. |
- Gao, J. T., et al.
(författare)
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Feasibility and economic analysis of solution transportation absorption system for long-distance thermal transportation under low ambient temperature
- 2019
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Ingår i: Energy Conversion and Management. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0196-8904 .- 1879-2227. ; 196, s. 793-806
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Tidskriftsartikel (refereegranskat)abstract
- Sensible heat transportation with water is widely adopted in traditional heating network, which suffers from the low energy transportation density and inevitable heat loss for long-distance heat transportation. To address these two issues, the solution transportation absorption system has been proposed, which transports the thermal energy by stable chemical potential. However, boundary between the two technologies is not clear due to the lack of direct comparison on both technological and economic aspects. In this work, feasibility analysis of the solution transportation absorption system is performed using Aspen plus, and low ambient temperature is considered for a practical scenario. Economic contrast is performed by exergoeconomic analysis. Results show that the coefficient of performance and exergy efficiency of the solution transportation absorption system can reach 0.556 and 24.6% in optimal condition. The energy transportation density is nearly three times higher than that of traditional sensible heat transportation. Moreover, the exergoeconomic analysis indicates that the new system is more economical when the distance exceeds 6 km. It has been proved that the solution transportation absorption system is a feasible and economical way to efficiently transport thermal energy over long distance.
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