101 research outputs found
U.S. Naval Observatory VLBI Analysis Center
This report summarizes the activities of the VLBI Analysis Center at the United States Naval Observatory for the 2012 calendar year. Over the course of the year, Analysis Center personnel continued analysis and timely submission of IVS-R4 databases for distribution to the IVS. During the 2012 calendar year, the USNO VLBI Analysis Center produced two VLBI global solutions designated as usn2012a and usn2012b. Earth orientation parameters (EOP) based on this solution and updated by the latest diurnal (IVS-R1 and IVS-R4) experiments were routinely submitted to the IVS. Sinex files based upon the bi-weekly 24-hour experiments were also submitted to the IVS. During the 2012 calendar year, Analysis Center personnel continued a program to use the Very Long Baseline Array (VLBA) operated by the NRAO for the purpose of measuring UT1-UTC. Routine daily 1-hour duration Intensive observations were initiated using the VLBA antennas at Pie Town, NM and Mauna Kea, HI. High-speed network connections to these two antennas are now routinely used for electronic transfer of VLBI data over the Internet to a USNO point of presence. A total of 270 VLBA Intensive experiments were observed and electronically transferred to and processed at USNO in 2012
Toward the Potential Scale-Up of SnMnO||LiNiMnCoO Li-Ion Batteries – Powering a RemoteControlled Vehicle and Life Cycle Assessment
Academic research in the battery field frequently remains limited to small coin or pouch cells, especially for new materials that are still rather far from commercialization, which renders a meaningful evaluation at an early stage of development challenging. Here, the realization of large lab-scale pouch cells comprising SnMnO (SMO), prepared via an easily scalable hydrothermal synthesis method, as an alternative active material for the negative electrode and LiNiMnCoO (NMC) as a commercially available active material for the positive electrode is reported. Nine double-layer pouch cells are connected in series and parallel, suitable for powering a remote-controlled vehicle. Subsequently, these SMO‖NMC cells are critically evaluated by means of an early-stage life cycle assessment and compared to graphite‖NMC cells, in order to get first insights into the potential advantages and challenges of such lithium-ion chemistry
Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.
We report a technique to selectively and continuously label the proteomes of individual cell types in coculture, named cell type-specific labeling using amino acid precursors (CTAP). Through transgenic expression of exogenous amino acid biosynthesis enzymes, vertebrate cells overcome their dependence on supplemented essential amino acids and can be selectively labeled through metabolic incorporation of amino acids produced from heavy isotope-labeled precursors. When testing CTAP in several human and mouse cell lines, we could differentially label the proteomes of distinct cell populations in coculture and determine the relative expression of proteins by quantitative mass spectrometry. In addition, using CTAP we identified the cell of origin of extracellular proteins secreted from cells in coculture. We believe that this method, which allows linking of proteins to their cell source, will be useful in studies of cell-cell communication and potentially for discovery of biomarkers
SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration
High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation
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Assessing the impacts of 1.5 °C global warming – simulation protocol of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2b)
In Paris, France, December 2015, the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) invited the Intergovernmental Panel on Climate Change (IPCC) to provide a "special report in 2018 on the impacts of global warming of 1.5°C above pre-industrial levels and related global greenhouse gas emission pathways". In Nairobi, Kenya, April 2016, the IPCC panel accepted the invitation. Here we describe the response devised within the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) to provide tailored, cross-sectorally consistent impact projections to broaden the scientific basis for the report. The simulation protocol is designed to allow for (1) separation of the impacts of historical warming starting from pre-industrial conditions from impacts of other drivers such as historical land-use changes (based on pre-industrial and historical impact model simulations); (2) quantification of the impacts of additional warming up to 1.5°C, including a potential overshoot and long-term impacts up to 2299, and comparison to higher levels of global mean temperature change (based on the low-emissions Representative Concentration Pathway RCP2.6 and a no-mitigation pathway RCP6.0) with socio-economic conditions fixed at 2005 levels; and (3) assessment of the climate effects based on the same climate scenarios while accounting for simultaneous changes in socio-economic conditions following the middle-of-the-road Shared Socioeconomic Pathway (SSP2, Fricko et al., 2016) and in particular differential bioenergy requirements associated with the transformation of the energy system to comply with RCP2.6 compared to RCP6.0. With the aim of providing the scientific basis for an aggregation of impacts across sectors and analysis of cross-sectoral interactions that may dampen or amplify sectoral impacts, the protocol is designed to facilitate consistent impact projections from a range of impact models across different sectors (global and regional hydrology, lakes, global crops, global vegetation, regional forests, global and regional marine ecosystems and fisheries, global and regional coastal infrastructure, energy supply and demand, temperature-related mortality, and global terrestrial biodiversity)
Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research
A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer
Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
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