Cassandra Adams

Circulating plasma proteins play key roles in human health and can potentially be used to measure biological age, allowing risk prediction for age-related diseases, multimorbidity and mortality. Here we developed a proteomic age clock in the UK Biobank (n = 45,441) using a proteomic platform comprising 2,897 plasma proteins and explored its utility to predict major disease morbidity and mortality in diverse populations. We identified 204 proteins that accurately predict chronological age (Pearson r = 0.94) and found that proteomic aging was associated with the incidence of 18 major chronic diseases (including diseases of the heart, liver, kidney and lung, diabetes, neurodegeneration and cancer), as well as with multimorbidity and all-cause mortality risk. Proteomic aging was also associated with age-related measures of biological, physical and cognitive function, including telomere length, frailty index and reaction time. Proteins contributing most substantially to the proteomic age clock are involved in numerous biological functions, including extracellular matrix interactions, immune response and inflammation, hormone regulation and reproduction, neuronal structure and function and development and differentiation. In a validation study involving biobanks in China (n = 3,977) and Finland (n = 1,990), the proteomic age clock showed similar age prediction accuracy (Pearson r = 0.92 and r = 0.94, respectively) compared to its performance in the UK Biobank. Our results demonstrate that proteomic aging involves proteins spanning multiple functional categories and can be used to predict age-related functional status, multimorbidity and mortality risk across geographically and genetically diverse populations.

Abstract Ionising radiation (IR) is a recognised carcinogen responsible for cancer development in patients previously treated using radiotherapy, and in individuals exposed as a result of accidents at nuclear energy plants. However, the mutational signatures induced by distinct types and doses of radiation are unknown. Here, we analyse the genetic architecture of mammary tumours, lymphomas and sarcomas induced by high ( 56 Fe-ions) or low (gamma) energy radiation in mice carrying Trp53 loss of function alleles. In mammary tumours, high-energy radiation is associated with induction of focal structural variants, leading to genomic instability and Met amplification. Gamma-radiation is linked to large-scale structural variants and a point mutation signature associated with oxidative stress. The genomic architecture of carcinomas, sarcomas and lymphomas arising in the same animals are significantly different. Our study illustrates the complex interactions between radiation quality, germline Trp53 deficiency and tissue/cell of origin in shaping the genomic landscape of IR-induced tumours.

DESIGN PRINCIPLES. A New Context for Building Codes and Regulation (D. Eisenberg). Natural Conditioning of Buildings (K. Haggard, et al.). Structural Properties of Alternative Building Materials (B. King). SYSTEMS AND MATERIALS. Adobe (M. Moquin). Cob (M. Smith). Rammed Earth (D. Easton). Modular Contained Earth (J. Kennedy, et al.). Light Clay (R. Laporte & F. Andresen). Straw-Bale (K. Lerner, et al.). Bamboo (D. DeBoer & K. Bareis). Earthen Finishes (C. Crews, et al.). APPLICATIONS. Integrated Systems with Rammed Earth (M. Webster-Mannison). Straw, Clay, and Carrizo (B. Steen & A. Steen). Light-Clay House Additions (L. Host-Jablonski). Variations on Earthbag (K. Hunter, et al.). The Value of Indigenous Ways (C. Nelson). Building Technology Transfer (K. Lerner, et al.). Epilogue: Finding the Soul of Natural Building (T. Bender). Appendices. About the Contributors. Index.

Japan's Ise Shrine is famous for its thirteen-hundred-year-old reconstruction tradition, the Shikinen sengu, in which the most sacred structures are completely rebuilt every twenty years. The construction process incorporates not only the usual elements of planning, materials procurement, and installation, but also integrates some thirty Shinto rituals that mark important milestones in the construction process. This renewal is remarkable because it preserves an ancient architectural style that is extremely susceptible to decay as well as the ancient construction technologies needed to build it. Because each cycle is very closely modeled on its predecessor, the most recent reconstruction, completed in 1993, provides a window through which we can examine ancient construction attitudes and technologies.