Loss of Prolyl Hydroxylase-1 Protects Against Colitis Through Reduced Epithelial Cell Apoptosis and Increased Barrier Function

Background & Aims Hypoxia inducible factor (HIF) prolyl hydroxylase inhibitors are protective in mouse models of inflammatory bowel disease (IBD). Here, we investigated the therapeutic target(s) and mechanism(s) involved. Methods The effect of genetic deletion of individual HIF-prolyl hydroxylase (PHD) enzymes on the development of dextran sulphate sodium (DSS)induced colitis was examined in mice. Results PHD1-/-, but not PHD2+/- or PHD3-/-, mice were less susceptible to the development of colitis than wild-type controls as determined by weight loss, disease activity, colon histology, neutrophil infiltration, and cytokine expression. Reduced susceptibility of PHD1-/- mice to colitis was associated with increased density of colonic epithelial cells relative to wild-type controls, which was because of decreased levels of apoptosis that resulted in enhanced epithelial barrier function. Furthermore, with the use of cultured epithelial cells it was confirmed that hydroxylase inhibition reversed DSS-induced apoptosis and barrier dysfunction. Finally, PHD1 levels were increased with disease severity in intestinal tissue from patients with IBD and in colonic tissues from DSS-treated mice. Conclusions These results imply a role for PHD1 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon. Genetic loss of PHD1 is protective against colitis through decreased epithelial cell apoptosis and consequent enhancement of intestinal epithelial barrier function. Thus, targeted PHD1 inhibition may represent a new therapeutic approach in IBD. © 2010 AGA Institute

Use of model predictive control and weather forecasts for energy efficient building climate control

This paper presents an investigation of how ModelPredictiveControl (MPC) and weatherpredictions can increase the energy efficiency in Integrated Room Automation (IRA) while respecting occupant comfort. IRA deals with the simultaneous control of heating, ventilation and air conditioning (HVAC) as well as blind positioning and electric lighting of a building zone such that the room temperature as well as CO2 and luminance levels stay within given comfort ranges. MPC is an advanced control technique which, when applied to buildings, employs a model of the building dynamics and solves an optimization problem to determine the optimal control inputs. In this paper it is reported on the development and analysis of a Stochastic ModelPredictiveControl (SMPC) strategy for buildingclimatecontrol that takes into account the uncertainty due to the use of weatherpredictions. As first step the potential of MPC was assessed by means of a large-scale factorial simulation study that considered different types of buildings and HVAC systems at four representative European sites. Then for selected representative cases the control performance of SMPC, the impact of the accuracy of weatherpredictions, as well as the tunability of SMPC were investigated. The findings suggest that SMPC outperforms current control practice

Project house water: a novel interdisciplinary framework to assess the environmental and socioeconomic consequences of flood-related impacts

Abstract Protecting our water resources in terms of quality and quantity is considered one of the big challenges of the twenty-first century, which requires global and multidisciplinary solutions. A specific threat to water resources, in particular, is the increased occurrence and frequency of flood events due to climate change which has significant environmental and socioeconomic impacts. In addition to climate change, flooding (or subsequent erosion and run-off) may be exacerbated by, or result from, land use activities, obstruction of waterways, or urbanization of floodplains, as well as mining and other anthropogenic activities that alter natural flow regimes. Climate change and other anthropogenic induced flood events threaten the quantity of water as well as the quality of ecosystems and associated aquatic life. The quality of water can be significantly reduced through the unintentional distribution of pollutants, damage of infrastructure, and distribution of sediments and suspended materials during flood events. To understand and predict how flood events and associated distribution of pollutants may impact ecosystem and human health, as well as infrastructure, large-scale interdisciplinary collaborative efforts are required, which involve ecotoxicologists, hydrologists, chemists, geoscientists, water engineers, and socioeconomists. The research network “project house water” consists of a number of experts from a wide range of disciplines and was established to improve our current understanding of flood events and associated societal and environmental impacts. The concept of project house and similar seed fund and boost fund projects was established by the RWTH Aachen University within the framework of the German excellence initiative with support of the German research foundation (DFG) to promote and fund interdisciplinary research projects and provide a platform for scientists to collaborate on innovative, challenging research. Project house water consists of six proof-of-concept studies in very diverse and interdisciplinary areas of research (ecotoxicology, water, and chemical process engineering, geography, sociology, economy). The goal is to promote and foster high-quality research in the areas of water research and flood-risk assessments that combine and build off-laboratory experiments with modeling, monitoring, and surveys, as well as the use of applied methods and techniques across a variety of disciplines

Net ecosystem exchange

agricultural and forest meteorology 148 (2008) 821–838 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/agrformet Cross-site evaluation of eddy covariance GPP and RE decomposition technique