An engineered antibody fragment targeting mutant β-catenin via Major Histocompatibility
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99 GENERAL AND MISCELLANEOUS↗
Engineering topics
Miller, M
Publications and source records attributed to Miller, M.
SU-F-I-55: Performance Evaluation of Digital PET/CT: Medical Physics Basis for the Clinical Applications
Purpose: Replacement of conventional PMT-based detector with next generation digital photon counting (DPC) detector is a technology leap for PET imaging. This study evaluated the performance and characteristics of the DPC system and its stability within a 1 year time window following its installation focusing on the medical physics basis for clinical applications. Methods: A digital PET/CT scanner using 1:1 coupling of 23,040 crystal: detector elements was introduced and became operational at OSU. We tested and evaluated system performance and characteristics using NEMA NU2-2012. System stabilities in timing resolution, energy resolution, detector temperature and humidity (T&H) were monitored over 1-yr. Timing, energy and spatial resolution were characterized across clinically relevant count rate range. CQIE uniformity PET and NEMA IEC-Body PET with hot spheres varying with sizes and contrasts were performed. PET reconstructed in standard(4mm), High(2mm) and Ultra-High(1mm) definitions were evaluated. Results: NEMA results showed PET spatial resolution (mm-FWHM) from 4.01&4.14 at 1cm to 5.82&6.17 at 20cm in transverse & axial. 322±3ps timing and 11.0% energy resolution were measured. 5.7kcps/MBq system sensitivity with 24kcps/MBq effective sensitivity was obtained. The peak-NECR was ∼171kcps with the effective peak-NECR >650kcps@50kBq/mL. Scatter fraction was ∼30%, and the maximum trues was >900kcps. NEMA IQ demonstrated hot sphere contrast ranging from ∼62%±2%(10mm) to ∼88%±2%(22mm), cold sphere contrast of ∼86%±2%(28mm) and ∼89%±3%(37mm) and excellent uniformity. Monitoring 1-yr stability, it revealed ∼1% change in timing, ±0.4% change in energy resolution, and <10% variations in T&H. CQIE PET gave <3% SUV variances in axial. 60%–100% recovery coefficients across sphere sizes and contrast levels were achieved. Conclusion: Characteristics and stability of the next generation DPC PET detector system over an 1-yr time window was excellent and better than prior experiences. It demonstrated improved and robust system characteristics and performance in spatial resolution, sensitivity, timing and energy resolution, count rate and image quality. Michael Miller is an employee of Philips Healthcare.
60 APPLIED LIFE SCIENCES↗
Structural basis of RNA recognition and activation by innate immune receptor RIG-I
Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM.
59 BASIC BIOLOGICAL SCIENCES↗
Transformation of Southern California's Residential Photovoltaics Market Through Third-Party Ownership
Third-party photovoltaics (PV) ownership is a rapidly growing market trend, where commercial companies own and operate customer-sited PV systems and lease PV equipment or sell PV electricity to the building occupant. Third-party PV companies can reduce or eliminate up-front adoption costs, reduce technology risk and complexity by monitoring system performance, and can repackage the PV value proposition by showing cost savings in the first month of ownership rather than payback times on the order of a decade. We find that the entrance of third-party business models in southern California residential PV markets has enticed a new demographic to adopt PV systems that is more highly correlated to younger, less affluent, and less educated populations than the demographics correlated to purchasing PV systems. By enticing new demographics to adopt PV, we find that third-party PV products are likely increasing total PV demand rather than gaining market share entirely at the expense of existing customer owned PV demand. We also find that mean population demographics are good predictors of third-party and customer owned PV adoption, and mean voting trends on California carbon policy (Proposition 23) are poor predictors of PV adoption.
14 SOLAR ENERGY↗
High-energy diffraction microscopy at the advanced photon source
The status of the High Energy Diffraction Microscopy (HEDM) program at the 1-ID beam line of the Advanced Photon Source is reported. HEDM applies high energy synchrotron radiation for the grain and sub-grain scale structural and mechanical characterization of polycrystalline bulk materials in situ during thermomechanical loading. Case studies demonstrate the mapping of grain boundary topology, the evaluation of stress tensors of individual grains during tensile deformation and comparison to a finite element modeling simulation, and the characterization of evolving dislocation structure. Complementary information is obtained by post mortem electron microscopy on the same sample volume previously investigated by HEDM.
43 PARTICLE ACCELERATORS↗
Tropical and subtropical cloud transitions in weather and climate prediction models: the GCSS/WGNE Pacific Cross-Section Intercomparison (GPCI)
A model evaluation approach is proposed where weather and climate prediction models are analyzed along a Pacific Ocean cross-section, from the stratocumulus regions off the coast of California, across the shallow convection dominated trade-winds, to the deep convection regions of the ITCZ: the GCSS/WGNE Pacific Cross-section Intercomparison (GPCI). The main goal of GPCI is to evaluate, and help understand and improve the representation of tropical and sub-tropical cloud processes in weather and climate prediction models. In this paper, a detailed analysis of cloud regime transitions along the cross-section from the sub-tropics to the tropics for the season JJA of 1998 is presented. This GPCI study confirms many of the typical weather and climate prediction model problems in the representation of clouds: underestimation of clouds in the stratocumulus regime by most models with the corresponding consequences in terms of shortwave radiation biases; overestimation of clouds by the ECMWF Re-Analysis (ERA40) in the deep tropics (in particular) with the corresponding impact in the outgoing longwave radiation; large spread between the different models in terms of cloud cover, liquid water path and shortwave radiation; significant differences between the models in terms of vertical crosssections of cloud properties (in particular), vertical velocity and relative humidity. An alternative analysis of cloud cover mean statistics is proposed where sharp gradients in cloud cover along the GPCI transect are taken into account. This analysis shows that the negative cloud bias of some models and ERA40 in the stratocumulus regions (as compared to ISCCP) is associated not only with lower values of cloud cover in these regimes, but also with a stratocumulus-to-cumulus transition that occurs too early along the trade-wind Lagrangian trajectory. Histograms of cloud cover along the cross-section differ significantly between models. Some models exhibit a quasi-bimodal structure with cloud cover being either very large (close to 100%) or very small, while other models show a more continuous transition. The ISCCP observations suggest that reality is in-between these two extreme examples. These different patterns reflect the diverse nature of the cloud, boundary layer, and convection parameterizations in the participating weather and climate prediction models.
54 ENVIRONMENTAL SCIENCES↗