Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent state of cell cycle arrest accompanied by a secretory phenotype which contributes to inflammation and tissue deterioration. Genotoxic stresses, including radiation-induced DNA damage, are known to induce a senescence response. Here, we show that radiation induces cellular senescence preferentially in the salivary gland stem/progenitor cell niche of mouse models and patients. Similarly, salivary gland-derived organoids show increased expression of senescence markers and pro-inflammatory senescence-associated secretory phenotype (SASP) factors after radiation exposure. Clearance of senescent cells by selective removal of p16Ink4a-positive cells by the drug ganciclovir or the senolytic drug ABT263 lead to increased stem cell self-renewal capacity as measured by organoid formation efficiency. Additionally, pharmacological treatment with ABT263 in mice irradiated to the salivary glands mitigates tissue degeneration, thus preserving salivation. Our data suggest that senescence in the salivary gland stem/progenitor cell niche contributes to radiation-induced hyposalivation. Pharmacological targeting of senescent cells may represent a therapeutic strategy to prevent radiotherapy-induced xerostomia.
Building information modeling (BIM) is the digital representation of physical and functional characteristics (such as geometry, spatial relationship, and geographic information) of a facility to support decisions during its life cycle. BIM has been extended beyond 3D geometrical representations in recent years, and now includes time as a fourth dimension and cost as a fifth dimension, as well as such other applications as virtual reality and augmented reality. The Internet of Things (IoT) has been increasingly applied in various products (smart homes, wearables) to enhance work productivity, living comfort, and entertainment. However, research addressing the integration of these two technologies (BIM and IoT) is still very limited, and has focused exclusively on the automatic transmission of sensor information to BIM models. This paper describes an attempt to represent and visualize sensor data in BIM with multiple perspectives in order to support complex decisions requiring interdisciplinary information. The study uses a university campus as an example and includes several scenarios, such as an auditorium with a dispersed audience and energy-saving options for rooms with different functions (mechanical/electrical equipment, classrooms, and laboratory). This paper also discusses the design of a common platform allowing communication among sensors with different protocols (Arduino, Raspberry Pi), the use of Dynamo to accept sensor data as input and automatically redraw visualized information in BIM, and how visualization may help in making energy-saving management decisions.
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