IEA EBC Annex 72: Assessing Life Cycle Related Environmental Impacts Caused by Buildings: Guidelines for design decision-makers:Energy in Buildings and Communities Technology Collaboration Programme

The purpose of this report is to provide support to the design decisions-makers during the design process. For each of the defined design step decision the important topics to consider were identified, the key stakeholders are declared and the purpose of LCA at the selected design step is defined. The report covers: The definition of the design steps, the definition of the tasks in each design step and an overview of the relevant milestones for performing LCA; An overview of the systematic building decomposition methods and the appropriate levels at each design step; An overview of the tools that can be used for LCA and a selection process for choosing the right LCA tool. A special emphasize is given to the topic of Building Information Modelling (BIM), how the BIM tools can facilitate the LCA assessment and what information should be implemented in the BIM model; Strategies on how to reduce the design-related uncertainties; An overview of the visualization of the LCA results and which are appropriate in the selected design steps

A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) represents the most common liver disease in Western countries and often progresses to non-alcoholic steatohepatitis (NASH) leading ultimately to liver fibrosis and liver cancer. The occurrence of hepatocyte cell deathso far characterized as hepatocyte apoptosisrepresents a fundamental step from benign steatosis toward progressive steatohepatitis. In contrast, the function of RIP3-dependent necroptosis in NASH and NASH-induced fibrosis is currently unknown. We show that RIP3 is upregulated in human NASH and in a dietary mouse model of steatohepatitis. RIP3 mediates liver injury, inflammation, induction of hepatic progenitor cells/activated cholangiocytes, and liver fibrosis through a pathway suppressed by Caspase-8. This function of RIP3 is mediated by a positive feedback loop involving activation of Jun-(N)-terminal Kinase (JNK). Furthermore, RIP3-dependent JNK activation promotes the release of pro-inflammatory mediators like MCP-1, thereby attracting macrophages to the injured liver and further augmenting RIP3-dependent signaling, cell death, and liver fibrosis. Thus, RIP3-dependent necroptosis controls NASH-induced liver fibrosis. This pathway might represent a novel and specific target for pharmacological strategies in patients with NASH