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High-resolution, global quantification of fossil fuel CO[subscript 2] emissions is emerging as a critical need in carbon cycle science and climate policy. We build upon a previously developed fossil fuel data assimilation system (FFDAS) for estimating global high-resolution fossil fuel CO[subscript 2] emissions. We have improved the underlying observationally based

High-resolution, global quantification of fossil fuel CO[subscript 2] emissions is emerging as a critical need in carbon cycle science and climate policy. We build upon a previously developed fossil fuel data assimilation system (FFDAS) for estimating global high-resolution fossil fuel CO[subscript 2] emissions. We have improved the underlying observationally based data sources, expanded the approach through treatment of separate emitting sectors including a new pointwise database of global power plants, and extended the results to cover a 1997 to 2010 time series at a spatial resolution of 0.1°. Long-term trend analysis of the resulting global emissions shows subnational spatial structure in large active economies such as the United States, China, and India. These three countries, in particular, show different long-term trends and exploration of the trends in nighttime lights, and population reveal a decoupling of population and emissions at the subnational level. Analysis of shorter-term variations reveals the impact of the 2008–2009 global financial crisis with widespread negative emission anomalies across the U.S. and Europe. We have used a center of mass (CM) calculation as a compact metric to express the time evolution of spatial patterns in fossil fuel CO[subscript 2] emissions. The global emission CM has moved toward the east and somewhat south between 1997 and 2010, driven by the increase in emissions in China and South Asia over this time period. Analysis at the level of individual countries reveals per capita CO[subscript 2] emission migration in both Russia and India. The per capita emission CM holds potential as a way to succinctly analyze subnational shifts in carbon intensity over time. Uncertainties are generally lower than the previous version of FFDAS due mainly to an improved nightlight data set.

ContributorsAsefi-Najafabady, Salvi (Author) / Rayner, P. J. (Author) / Gurney, Kevin (Author) / McRobert, A. (Author) / Song, Y. (Author) / Coltin, K. (Author) / Huang, J. (Author) / Elvidge, C. (Author) / Baugh, K. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-09-16
Description

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV.

Created2015-05-01
Description

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma.

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy.

Created2015-04-01
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Description

Many municipal governments have adopted affordable housing policies to benefit people whose socio-economic status is not commensurate with the price of housing. However, the effects and the functions of these policies in the city on sustainable development and living remains limited. Using a comparative case study, this study explores the

Many municipal governments have adopted affordable housing policies to benefit people whose socio-economic status is not commensurate with the price of housing. However, the effects and the functions of these policies in the city on sustainable development and living remains limited. Using a comparative case study, this study explores the characteristics and effects of affordable housing policies in three metropolitan cities in China: Beijing, Tianjin, and Guangshou. This study finds that these cities have their unique affordable housing policies and have experienced various challenges in implementing those policies. Conclusions and implications for other cities in China are addressed.

ContributorsCai, Xiang (Author) / Tsai, Chin-Chang (Author) / Wu, Wei-Ning (Author) / College of Public Service and Community Solutions (Contributor)
Created2017-04-01
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Description

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide.

Methods: Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included.

Results: Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent.

Conclusion: Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.

ContributorsBurden, Christy (Author) / Bradley, Stephanie (Author) / Storey, Claire (Author) / Ellis, Alison (Author) / Heazell, Alexander E. P. (Author) / Downe, Soo (Author) / Cacciatore, Joanne (Author) / Siassakos, Dimitrios (Author) / College of Public Service and Community Solutions (Contributor)
Created2016-01-19
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Description

Large urban emissions of greenhouse gases result in large atmospheric enhancements relative to background that are easily measured. Using CO2 mole fractions and Δ14C and δ13C values of CO2 in the Los Angeles megacity observed in inland Pasadena (2006–2013) and coastal Palos Verdes peninsula (autumn 2009–2013), we have determined time

Large urban emissions of greenhouse gases result in large atmospheric enhancements relative to background that are easily measured. Using CO2 mole fractions and Δ14C and δ13C values of CO2 in the Los Angeles megacity observed in inland Pasadena (2006–2013) and coastal Palos Verdes peninsula (autumn 2009–2013), we have determined time series for CO2 contributions from fossil fuel combustion (Cff) for both sites and broken those down into contributions from petroleum and/or gasoline and natural gas burning for Pasadena. We find a 10 % reduction in Pasadena Cff during the Great Recession of 2008–2010, which is consistent with the bottom-up inventory determined by the California Air Resources Board. The isotopic variations and total atmospheric CO2 from our observations are used to infer seasonality of natural gas and petroleum combustion. The trend of CO2 contributions to the atmosphere from natural gas combustion is out of phase with the seasonal cycle of total natural gas combustion seasonal patterns in bottom-up inventories but is consistent with the seasonality of natural gas usage by the area's electricity generating power plants. For petroleum, the inferred seasonality of CO2 contributions from burning petroleum is delayed by several months relative to usage indicated by statewide gasoline taxes. Using the high-resolution Hestia-LA data product to compare Cff from parts of the basin sampled by winds at different times of year, we find that variations in observed fossil fuel CO2 reflect seasonal variations in wind direction. The seasonality of the local CO2 excess from fossil fuel combustion along the coast, on Palos Verdes peninsula, is higher in autumn and winter than spring and summer, almost completely out of phase with that from Pasadena, also because of the annual variations of winds in the region. Variations in fossil fuel CO2 signals are consistent with sampling the bottom-up Hestia-LA fossil CO2 emissions product for sub-city source regions in the LA megacity domain when wind directions are considered.

ContributorsNewman, Sally (Author) / Xu, Xiaomei (Author) / Gurney, Kevin (Author) / Hsu, Ying Kuang (Author) / Li, King Fai (Author) / Jiang, Xun (Author) / Keeling, Ralph (Author) / Feng, Sha (Author) / O'Keeffe, Darragh (Author) / Patarasuk, Risa (Author) / Wong, Kam Weng (Author) / Rao, Preeti (Author) / Fischer, Marc L. (Author) / Yung, Yuk L. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-03-22
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Description

Cervical cancer is the most common malignancy among women particularly in developing countries, with human papillomavirus (HPV) 16 causing 50% of invasive cervical cancers. A plant-based HPV vaccine is an alternative to the currently available virus-like particle (VLP) vaccines, and would be much less expensive. We optimized methods to express

Cervical cancer is the most common malignancy among women particularly in developing countries, with human papillomavirus (HPV) 16 causing 50% of invasive cervical cancers. A plant-based HPV vaccine is an alternative to the currently available virus-like particle (VLP) vaccines, and would be much less expensive. We optimized methods to express HPV16 L1 protein and purify VLPs from tobacco (Nicotiana benthamiana) leaves transfected with the magnICON deconstructed viral vector expression system. L1 proteins were extracted from agro-infiltrated leaves using a series of pH and salt mediated buffers. Expression levels of L1 proteins and VLPs were verified by immunoblot and ELISA, which confirmed the presence of sequential and conformational epitopes, respectively. Among three constructs tested (16L1d22, TPL1d22, and TPL1F), TPL1F, containing a full-length L1 and chloroplast transit peptide, was best. Extraction of HPV16 L1 from leaf tissue was most efficient (> 2.5% of total soluble protein) with a low-salt phosphate buffer. VLPs were purified using both cesium chloride (CsCl) density gradient and size exclusion chromatography. Electron microscopy studies confirmed the presence of assembled forms of HPV16 L1 VLPs. Collectively; our results indicated that chloroplast-targeted transient expression in tobacco plants is promising for the production of a cheap, efficacious HPV16 L1 VLP vaccine. Studies are underway to develop plant VLPs for the production of a cervical cancer vaccine.

ContributorsZahin, Maryam (Author) / Joh, Joongho (Author) / Khanal, Sujita (Author) / Husk, Adam (Author) / Mason, Hugh (Author) / Warzecha, Heribert (Author) / Ghim, Shin-je (Author) / Miller, Donald M. (Author) / Matoba, Nobuyuki (Author) / Bennett Jenson, Alfred (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2016-08-12
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Description

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after the in vivo administration of A. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γ and tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role of A. membranaceus in priming for a potential immune response as well as its effect on blood flow and wound healing.

Created2016-03-30
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Description

We previously reported a recombinant protein production system based on a geminivirus replicon that yields high levels of vaccine antigens and monoclonal antibodies in plants. The bean yellow dwarf virus (BeYDV) replicon generates massive amounts of DNA copies, which engage the plant transcription machinery. However, we noticed a disparity between

We previously reported a recombinant protein production system based on a geminivirus replicon that yields high levels of vaccine antigens and monoclonal antibodies in plants. The bean yellow dwarf virus (BeYDV) replicon generates massive amounts of DNA copies, which engage the plant transcription machinery. However, we noticed a disparity between transcript level and protein production, suggesting that mRNAs could be more efficiently utilized. In this study, we systematically evaluated genetic elements from human, viral, and plant sources for their potential to improve the BeYDV system. The tobacco extensin terminator enhanced transcript accumulation and protein production compared to other commonly used terminators, indicating that efficient transcript processing plays an important role in recombinant protein production.

Evaluation of human-derived 5′ untranslated regions (UTRs) indicated that many provided high levels of protein production, supporting their cross-kingdom function. Among the viral 5′ UTRs tested, we found the greatest enhancement with the tobacco mosaic virus omega leader. An analysis of the 5′ UTRs from the Arabidopsis thaliana and Nicotinana benthamiana photosystem I K genes found that they were highly active when truncated to include only the near upstream region, providing a dramatic enhancement of transgene production that exceeded that of the tobacco mosaic virus omega leader. The tobacco Rb7 matrix attachment region inserted downstream from the gene of interest provided significant enhancement, which was correlated with a reduction in plant cell death. Evaluation of Agrobacterium strains found that EHA105 enhanced protein production and reduced cell death compared to LBA4301 and GV3101. We used these improvements to produce Norwalk virus capsid protein at >20% total soluble protein, corresponding to 1.8 mg/g leaf fresh weight, more than twice the highest level ever reported in a plant system. We also produced the monoclonal antibody rituximab at 1 mg/g leaf fresh weight.

ContributorsDiamos, Andy (Author) / Rosenthal, Sun (Author) / Mason, Hugh (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2016-02-24
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Description

Atmospheric CO2 inversions estimate surface carbon fluxes from an optimal fit to atmospheric CO2 measurements, usually including prior constraints on the flux estimates. Eleven sets of carbon flux estimates are compared, generated by different inversions systems that vary in their inversions methods, choice of atmospheric data, transport model and prior

Atmospheric CO2 inversions estimate surface carbon fluxes from an optimal fit to atmospheric CO2 measurements, usually including prior constraints on the flux estimates. Eleven sets of carbon flux estimates are compared, generated by different inversions systems that vary in their inversions methods, choice of atmospheric data, transport model and prior information. The inversions were run for at least 5 yr in the period between 1990 and 2010. Mean fluxes for 2001–2004, seasonal cycles, interannual variability and trends are compared for the tropics and northern and southern extra-tropics, and separately for land and ocean. Some continental/basin-scale subdivisions are also considered where the atmospheric network is denser. Four-year mean fluxes are reasonably consistent across inversions at global/latitudinal scale, with a large total (land plus ocean) carbon uptake in the north (−3.4 Pg C yr-1 (±0.5 Pg C yr-1 standard deviation), with slightly more uptake over land than over ocean), a significant although more variable source over the tropics (1.6 ± 0.9 Pg C yr-1) and a compensatory sink of similar magnitude in the south (−1.4 ± 0.5 Pg C yr-1) corresponding mainly to an ocean sink. Largest differences across inversions occur in the balance between tropical land sources and southern land sinks. Interannual variability (IAV) in carbon fluxes is larger for land than ocean regions (standard deviation around 1.06 versus 0.33 Pg C yr[superscript −1] for the 1996–2007 period), with much higher consistency among the inversions for the land. While the tropical land explains most of the IAV (standard deviation ~ 0.65 Pg C yr-1), the northern and southern land also contribute (standard deviation ~ 0.39 Pg C yr-1). Most inversions tend to indicate an increase of the northern land carbon uptake from late 1990s to 2008 (around 0.1 Pg C yr-1, predominantly in North Asia. The mean seasonal cycle appears to be well constrained by the atmospheric data over the northern land (at the continental scale), but still highly dependent on the prior flux seasonality over the ocean. Finally we provide recommendations to interpret the regional fluxes, along with the uncertainty estimates.

ContributorsPeylin, P. (Author) / Law, R. M. (Author) / Gurney, Kevin (Author) / Chevallier, F. (Author) / Jacobson, A. R. (Author) / Maki, T. (Author) / Niwa, Y. (Author) / Patra, P. K. (Author) / Peters, W. (Author) / Rayner, P. J. (Author) / Rodenbeck, C. (Author) / van der Laan-Luijkx, I. T. (Author) / Zhang, X. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-10-24