Advanced Energy Retrofit - Designing Integrated Design Roadmaps

Today’s commercial building market can ill afford the renovation of buildings by industry professionals that use archaic methods and uniformed approaches that neglect to account for the building’s energy consumption. This paper advances a comprehensive solution for minimizing energy consumption in existing small to medium-sized commercial buildings. Committed to increasing the number of advanced energy retrofits completed in the United States over the next 20 years, this research team has over the past two years developed an Integrated Design Roadmap for advanced energy retrofits designed to assist project teams and building owners in achieving deep energy savings in the renovation of existing buildings. The paper’s content was produced as part of a research initiative of the Consortium for Building Energy Innovation (formerly the Energy Efficient Buildings Hub) and sponsored by the United States (US) Department of Energy since 2011. The Integrated Design (ID) Advanced Energy Retrofit (AER) Roadmap discussed in this paper contains a series of process documents of use to owners, project managers, financial investors, architecture, engineering, and construction (AEC) professionals, as well as energy modeling and measurement consultants involved in the completion of an AER, with targeted savings of 50% energy use against its pre-retrofit baseline consumption. This paper will describe the preliminary research required in the design of the ID AER Roadmap, as well as the overall document suite. The ID AER Roadmap document suite includes an Overview brochure that introduces the principle ID concepts, as well as a Reference Manual that details these concepts, with the final component being a Project Team Guide of use to professionals in the building industry. The ID AER Roadmap document suite promotes the adoption of Integrated Design principles during the completion of an advanced energy retrofit. It identifies a set of seven process-based protocols key to the success of any AER, the details of which are described in this paper. The research which has served as a foundation for the Roadmap’s development includes a national survey of advanced energy retrofits completed in the US since the year 2000, a series of interviews of leading professionals who practice Integrated Design, and direct engagement with members of the AEC industry to introduce the Roadmap to a larger market audience

Functional Loss of Semaphorin 3C and/or Semaphorin 3D and Their Epistatic Interaction with Ret Are Critical to Hirschsprung Disease Liability

Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis