The balloon-borne Gamma-Ray Imager/Polarimeter for Solar flares (GRIPS) instrument will provide a near-optimal combination of high-resolution imaging, spectroscopy, and polarimetry of solar-flare gamma-ray/hard X-ray emissions from ~20 keV to >~10 MeV. GRIPS will address questions raised by recent solar flare observations regarding particle acceleration and energy release, such as: What causes the spatial separation between energetic electrons producing hard X-rays and energetic ions producing gamma-ray lines? How anisotropic are the relativistic electrons, and why can they dominate in the corona? How do the compositions of accelerated and ambient material vary with space and time, and why? The spectrometer/polarimeter consists of sixteen 3D position-sensitive germanium detectors (3D-GeDs), where each energy deposition is individually recorded with an energy resolution of a few keV FWHM and a spatial resolution of <0.1 mm 3 . Imaging is accomplished by a single multi-pitch rotating modulator (MPRM), a 2.5-cm thick tungstenalloy slit/slat grid with pitches that range quasi-continuously from 1 to 13 mm. The MPRM is situated 8 meters from the spectrometer to provide excellent image quality and unparalleled angular resolution at gamma-ray energies (12.5 arcsec FWHM), sufficient to separate 2.2 MeV footpoint sources for almost all flares. Polarimetry is accomplished by analyzing the anisotropy of reconstructed Compton scattering in the 3D-GeDs (i.e., as an active scatterer), with an estimated minimum detectable polarization of a few percent at 150-650 keV in an X-class flare. GRIPS is scheduled for a continental-US engineering test flight in fall 2013, followed by long or ultra-long duration balloon flights in Antarctica.
The Gamma-Ray Imager/Polarimeter for Solar flares (GRIPS) instrument is a balloon-borne telescope designed to study solar-flare particle acceleration and transport. We describe GRIPS's first Antarctic long-duration flight in January 2016 and report preliminary calibration and science results.Electron and ion dynamics, particle abundances and the ambient plasma conditions in solar flares can be understood by examining hard X-ray (HXR) and gamma-ray emission (20 keV to 10 MeV). Enhanced imaging, spectroscopy and polarimetry of flare emissions in this energy range are needed to study particle acceleration and transport questions. The GRIPS instrument is specifically designed to answer questions including: What causes the spatial separation between energetic electrons producing hard X-rays and energetic ions producing gamma-ray lines? How anisotropic are the relativistic electrons, and why can they dominate in the corona? How do the compositions of accelerated and ambient material vary with space and time, and why? GRIPS's key technological improvements over the current solar state of the art at HXR/gamma-ray energies, the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI), include 3D position-sensitive germanium detectors (3D-GeDs) and a single-grid modulation collimator, the multi-pitch rotating modulator (MPRM). The 3D-GeDs have spectral FWHM resolution of a few hundred keV and spatial resolution <1 mm 3 . For photons that Compton scatter, usually 150 keV, the energy deposition sites can be tracked, providing polarization measurements as well as enhanced background reduction through Compton imaging. Each of GRIPS's detectors has 298 electrode strips read out with ASIC/FPGA electronics. In GRIPS's energy range, indirect imaging methods provide higher resolution than focusing optics or Compton imaging techniques. The MPRM gridimaging system has a single-grid design which provides twice the throughput of a bi-grid imaging system like RHESSI. The grid is composed of 2.5 cm deep tungsten-copper slats, and quasi-continuous FWHM angular coverage from 12.5-162 arcsecs are achieved by varying the slit pitch between 1-13 mm. This angular resolution is capable of imaging the separate magnetic loop footpoint emissions in a variety of flare sizes. In comparison, RHESSI's 35-arcsec resolution at similar energies makes the footpoints resolvable in only the largest flares.
Alkenyl gold complexes are common intermediates in gold‐catalyzed transformations of allenes and alkynes, and numerous methods for their functionalization have been explored. Particularly valuable are cross‐coupling reactions, which result in the formation of a new C–C bond. Several strategies are known that enable α‐selective cross‐coupling of alkenyl gold complexes with aryl, allyl, or acyl coupling partners. We describe the direct β‐selective cross‐coupling of alkenyl gold complexes with simple alkyl electrophiles. We also describe the effects of the steric and electronic properties of alkenyl gold complexes on the selectivity of the cross‐coupling reaction.
Modification of effector function has proven to be an effective modality for optimizing activity and tolerability of therapeutic antibodies. Currently available methods to modulate effector function include the introduction of point mutations in the Fc region and glycan engineering of the antibody. Here we present an alternative and complementary method of tuning effector function utilizing a conjugation-based approach. This methodology uses conjugation of polyethylene glycol (PEG) to native cysteines of an antibody to impair FcγR binding of antibodies to innate immune effector cells. Utilizing maleimide or disulfide conjugation techniques, attenuated effector function can be either permanent or restored over time through a de-conjugation process. Impacts of PEGylation on FcγR binding, signaling, and restoration of function were assessed in vitro and in vivo. As a proof-of-concept, the lead technology was applied to an agonist CD40 antibody, which resulted in significant reductions in systemic cytokine production in hCD40 mice and non-human primates, while demonstrating retained efficacy and improved pharmacokinetics. Additionally, we combined the conjugation technology with glycan engineering and FcγR enhancing point mutations to impart unique effector function profiles to clinical antibodies. This simple, modular approach can be rapidly applied to existing antibodies to reduce immune-driven toxicities, such as infusion reactions, and optimize effector function activity.
Citation Format: Philip N. Moquist, Chris I. Leiske, Noah A. Bindman, Xinqun Zhang, Nicole Duncan, Weiping Zeng, Serena W. Wo, Abbie Wong, Clark M. Henderson, Karalyne Crowder, Haley D. Neff-LaFord, Django Sussman, Shyra J. Gardai, Matthew R. Levengood. Reversible chemical modification of antibodies: A complementary approach to tuning FcγR binding that maintains anti-tumor activity while mitigating peripheral immune activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2656.
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