471 research outputs found

    Space-Time Forecasting Using Soft Geostatistics: A Case Study in Forecasting Municipal Water Demand for Phoenix, AZ

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    Managing environmental and social systems in the face of uncertainty requires the best possible forecasts of future conditions. We use space-time variability in historical data and projections of future population density to improve forecasting of residential water demand in the City of Phoenix, Arizona. Our future water estimates are derived using the first and second order statistical moments between a dependent variable, water use, and an independent variable, population density. The independent variable is projected at future points, and remains uncertain. We use adjusted statistical moments that cover projection errors in the independent variable, and propose a methodology to generate information-rich future estimates. These updated estimates are processed in Bayesian Maximum Entropy (BME), which produces maps of estimated water use to the year 2030. Integrating the uncertain estimates into the space-time forecasting process improves forecasting accuracy up to 43.9% over other space-time mapping methods that do not assimilate the uncertain estimates. Further validation studies reveal that BME is more accurate than co-kriging that integrates the error-free independent variable, but shows similar accuracy to kriging with measurement error that processes the uncertain estimates. Our proposed forecasting method benefits from the uncertain estimates of the future, provides up-to-date forecasts of water use, and can be adapted to other socioeconomic and environmental applications.

    Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II

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    Background Aging and latent infection with Cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ subset is currently limited. Results Here, we have surveyed a population of 73 younger (23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+ populations in elderly CMV-seropositive individuals confirming the association of these Vδ2-negative cells with CMV-immunosurveillance. We identified the highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive individuals, who also possessed a lower naïve and a larger late-differentiated compartment of CD8+ αβ T-cells, reflecting the consensus in the literature. Conclusions Our findings illustrate in detail the strong influence of CMV on the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment, associated both with the presence of CMV and with age require further clarification

    The Influence of the CSU Robert Noyce Teacher Scholarship Program on Undergraduates\u27 Teaching Plans

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    The Robert Noyce Teacher Scholarship Program offers academic and financial support for students pursuing secondary teaching certificates in STEM fields. In return, students commit to teaching in high-need K-12 school districts. The Noyce Program has had uneven results in increasing the number of teachers in high needs schools. Large scale studies of its impact indicate the program is not likely to influence decisions to teach but may persuade participants to initially teach in high needs schools. To better understand the influence of the Noyce Program, we offer case studies of two Noyce scholarship recipients at different stages: (1) a former scholarship recipient who has graduated and is currently teaching, and (2) a second-year recipient who is currently pursuing a teaching certificate. This qualitative analysis provides insights that may have implications for optimizing scholarship programs for recruiting and retaining highly qualified STEM teachers

    Presentation of the Same Glycolipid by Different CD1 Molecules

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    Five CD1 molecules are expressed in humans and it is unclear whether they have specialized or redundant functions. We found that sulfatide is a promiscuous CD1-binding ligand and have isolated T cell clones that are specific for sulfatide and restricted by distinct CD1 molecules. These clones have been used to compare the capacity of different CD1 to present the same glycolipid, to induce effector functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c molecules similarly load sulfatide on the cell surface without processing, and prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much longer than that by CD1b and CD1c in living cells. Use of recombinant soluble CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other glycosphingolipids bind to all CD1, which suggests the presence of additional promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of self-glycolipids, even though they are quite divergent from an evolutionary point of view

    Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2(+) γδ T cell cytotoxicity in a perforin-dependent manner.

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    Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA. We differentiated peripheral blood monocytes from healthy donors into Mϕs and then treated them with IFN-γ or IL-4 to generate M1 and M2 Mϕs, respectively. We characterised these Mϕs based on their phenotype and cytokine production and then tested whether ZA rendered them susceptible to Vδ2(+) T cell cytotoxicity. Consistent with the literature, IFN-γ-treated Mϕs expressed higher levels of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mϕs expressed higher levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated with ZA, both M1 and M2 Mϕs became susceptible to Vδ2(+) T cell cytotoxicity. Vδ2(+) T cells expressed perforin and degranulated in response to ZA-treated Mϕs as shown by mobilisation of CD107a and CD107b to the cell surface. Furthermore, cytotoxicity towards ZA-treated Mϕs was sensitive-at least in part-to the perforin inhibitor concanamycin A. These findings suggest that ZA can render M1 and M2 Mϕs susceptible to Vδ2(+) T cell cytotoxicity in a perforin-dependent manner, which has important implications regarding the use of ZA in cancer immunotherapy
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