Browsing by Subject "proton"

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    GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia
    (Lippincott, Williams & Wilkins, 2020-12) Wang, Tao; Zhou, Guokun; He, Mindi; Xu, Yuanyuan; Rusyniak, W.G.; Xu, Yan; Ji, Yonghua; Simon, Roger P.; Xiong, Zhi-Gang; Zha, Xiang-ming; Obstetrics and Gynecology, School of Medicine
    Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury. Methods: We analyzed the expression of proton-sensitive GPCRs (G protein-coupled receptors) in the brain, examined acidosis-induced signaling in vitro, and studied neuronal injury using in vitro and in vivo mouse models. Results: GPR68, a proton-sensitive GPCR, was present in both mouse and human brain, and elicited neuroprotection in acidotic and ischemic conditions. GPR68 exhibited wide expression in brain neurons and mediated acidosis-induced PKC (protein kinase C) activation. PKC inhibition exacerbated pH 6-induced neuronal injury in a GPR68-dependent manner. Consistent with its neuroprotective function, GPR68 overexpression alleviated middle cerebral artery occlusion–induced brain injury. Conclusions: These data expand our knowledge on neuronal acid signaling to include a neuroprotective metabotropic dimension and offer GPR68 as a novel therapeutic target to alleviate neuronal injuries in ischemia and multiple other neurological diseases.
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    Rapid RBE-Weighted Proton Radiation Dosimetry Risk Assessment
    (Sage, 2016-10) Qutub, Mohammad A. Z.; Klein, Susan B.; Buchsbaum, Jeffrey C.; Department of Radiation Oncology, IU School of Medicine
    Proton therapy dose is affected by relative biological effectiveness differently than X-ray therapies. The current clinically accepted weighting factor is 1.1 at all positions along the depth–dose profile. However, the relative biological effectiveness correlates with the linear energy transfer, cell or tissue type, and the dose per fraction causing variation of relative biological effectiveness along the depth–dose profile. In this article, we present a simple relative biological effectiveness-weighted treatment planning risk assessment algorithm in 2-dimensions and compare the results with those derived using the standard relative biological effectiveness of 1.1. The isodose distribution profiles for beams were accomplished using matrices that represent coplanar intersecting beams. These matrices were combined and contoured using MATLAB to achieve the distribution of dose. There are some important differences in dose distribution between the dose profiles resulting from the use of relative biological effectiveness = 1.1 and the empirically derived depth-dependent values of relative biological effectiveness. Significant hot spots of up to twice the intended dose are indicated in some beam configurations. This simple and rapid risk analysis could quickly evaluate the safety of various dose delivery schema.