Orbital Gravity Gradiometry Beyond GOCE: Mission Concepts

Significant advances in the technologies needed for space-based cryogenic instruments have been made in the last decade, including cryocoolers, spacecraft architectures and cryogenic amplifiers. These enable considerably more complex instruments to be put into orbit for long-duration missions. One such instrument is the Superconducting Gravity Gradiometer (SGG) developed by Paik, et al. A magnetically levitated version is under consideration for a follow-on mission to GRACE (Gravity Recovery and Climate Experiment) and GOCE (Gravity field and steady-state Ocean Circulation Explorer). With its inherently greater rejection of common mode accelerations and ability to cancel the coupling of angular accelerations into the gradient signal, the SGG can achieve [an accuracy of] 0.01 milli-Eotvos (gravitational gradient of the Earth) divided by the square root of frequency in hertz, with requirements for attitude control that can be met with existing spacecraft. In addition, the use of a cryocooler for cooling the instrument will alleviate the previously severe constraint on mission lifetime imposed by the use of superfluid helium,. enabling mission durations in the 5-10 year range. Studies are underway to determine requirements for orbit (polar versus sun-synchronous), altitude (which affects spacecraft drag), instrument temperature and stability, cryocooler vibration control, and control and readout electronics. These will be used to determine the SGG's sensitivity and ultimate resolution for gravity recovery. This paper will discuss preliminary instrument and spacecraft design, and toplevel mission requirements

Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4

Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)