Field programmable gate arrays (FPGAs) are used in large numbers in data centers around the world. They are used for cloud computing and computer networking. The most common type of FPGA used in data centers are re-programmable SRAM-based FPGAs. These devices offer potential performance and power consumption savings. A single device also carries a small susceptibility to radiation-induced soft errors, which can lead to unexpected behavior. This article examines the impact of terrestrial radiation on FPGAs in data centers. Results from artificial fault injection and accelerated radiation testing on several data-center-like FPGA applications are compared. A new fault injection scheme provides results that are more similar to radiation testing. Silent data corruption (SDC) is the most commonly observed failure mode followed by FPGA unavailable and host unresponsive. A hypothetical deployment of 100,000 FPGAs in Denver, Colorado, will experience upsets in configuration memory every half-hour on average and SDC failures every 0.5–11 days on average.
Radiation-induced xerostomia, as a major problem in radiation treatment of the head and neck cancer, is mainly due to the overdose irradiation injury to the parotid glands. Helical Tomotherapy-based megavoltage computed tomography (MVCT) imaging during the Tomotherapy treatment can be applied to monitor the successive variations in the parotid glands. While manual segmentation is time consuming, laborious, and subjective, automatic segmentation is quite challenging due to the complicated anatomical environment of head and neck as well as noises in MVCT images. In this article, we propose a localization-refinement scheme to segment the parotid gland in MVCT. After data pre-processing we use mask region convolutional neural network (Mask R-CNN) in the localization stage after data pre-processing, and design a modified U-Net in the following fine segmentation stage. To the best of our knowledge, this study is a pioneering work of deep learning on MVCT segmentation. Comprehensive experiments based on different data distribution of head and neck MVCTs and different segmentation models have demonstrated the superiority of our approach in terms of accuracy, effectiveness, flexibility, and practicability. Our method can be adopted as a powerful tool for radiation-induced injury studies, where accurate organ segmentation is crucial.
Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD.Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used.Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor.Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.
AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.
Objectives To assess the outcomes of a conservative management approach to radiation-induced urethral stricture disease (R-USD) in an elderly population with comorbidities. Methods Patients with R-USD managed with endoscopic procedures and/or clean intermittent catheterization (CIC) between 2007 and 2019 were included. Patients were excluded if they had an obliterative stricture, prior urethral reconstruction/urinary diversion surgery, or < 3 months follow-up. Primary outcome measures were urinary tract infection (UTI), acute urinary retention (AUR), serum creatinine, uroflowmetry/post-void residual, and urinary incontinence (UI). Failure was defined as progression to reconstructive surgery or permanent indwelling catheterization. Results Ninety-one men were analyzed with a median follow-up of 15.0 months (IQR 8.9 to 37.9). Median age was 75.4 years (IQR 70.0 to 80.0), body mass index was 26.5 kg/m2 (IQR 24.8 to 30.3), and Charlson comorbidity index was 6 (IQR 5 to 8). Median stricture length was 2.0 cm (IQR 2.0 to 3.0). Stricture location was bulbar (12%), bulbomembranous (75%), and prostatic (13%). A total of 90% underwent dilation, and 44% underwent direct visual internal urethrotomy (DVIU). For those that underwent these procedures, median number of dilations and DVIUs per patient was 2 (IQR 1 to 5) and 1 (IQR 1 to 3), respectively. Forty percent used CIC. Thirty-four percent developed a UTI, and 15% had an AUR episode requiring urgent treatment. Creatinine values, uroflowmetry measurements, and UI rates remained stable. Eighty percent avoided reconstructive surgery or indwelling catheterization. Conclusion Most elderly patients with comorbidities with R-USD appear to be effectively managed in the short-term with conservative strategies. Close observation is warranted because of the risk of UTIs and AUR. The potential long-term consequences of repetitive conservative interventions must be considered.
Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mechanistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investigate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the morphological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined.