Integrated hydrological model-based assessment of stormwater management scenarios in Copenhagen's first climate resilient neighbourhood using the three point approach

The city of Copenhagen currently pursues a very ambitious plan to make the city ‘cloudburst proof’ within the next 30 years. The cloudburst management plan has the potential to support the city’s aim to become more green, liveable, and sustainable. In this study, we assessed stormwater system designs using the Three Point Approach (3PA) as a framework, where an indicator value for each domain was calculated using state-of-the-art modelling techniques. We demonstrated the methodology on scenarios representing sequential enhancements of the cloudburst management plan for a district that has been appointed to become the first climate resilient neighbourhood in Copenhagen. The results show that if the cloudburst system is exploited to discharge runoff from selected areas that are disconnected from the combined sewer system, then the plan leads to multiple benefits. These include improved flood protection under a 100-years storm (i.e., compliance with the new demands in domain C of the 3PA), reduced surcharge to terrain under a 10-years storm (i.e., compliance with the service goal in domain B of the 3PA) and an improved yearly water balance (i.e., better performance in domain A of the 3PA)

When Process Affects Punishment: Differences in Sentences After Guilty Plea, Bench Trial, and Jury Trial in Five Guidelines States

The research reported in this Essay examines process discounts-differences in sentences imposed for the same offense, depending upon whether the conviction was by jury trial, bench trial, or guilty plea-in five states that use judicial sentencing guidelines. Few guidelines systems expressly recognize plea agreement as an acceptable basis for departure, and none authorizes judges to vary sentences based upon whether or not the defendant waived his right to a jury trial and opted for a bench trial. Nevertheless, we predicted that because of the cost savings resulting from waivers, judges and prosecutors in any sentencing system would ensure that guilty plea convictions would generate the lowest sentences, with bench trial sentences averaging higher than plea-based sentences for the same offense, and sentences following jury trials averagingt he highest of all, even after controllingf or otherf actors associated with sentence severity. We found that a significant plea discount is evident for most offenses in all five states. Waiving a jury in favor of a bench trial has less consistent punishment consequences. Among states and even within a single state, the prevalence of process discounts is extraordinarily varied, as are the causes and methods of discounting. The Essay explores how these findings might inform sentencing reform and discusses the use of bench trials in sentencing guidelines systems generally

A Mapping of Tools for Informing Water Sensitive Urban Design Planning Decisions—Questions, Aspects and Context Sensitivity

Water Sensitive Urban Design (WSUD) poses new challenges for decision makers compared with traditional stormwater management, e.g., because WSUD offers a larger selection of measures and because many measures are multifunctional. These challenges have motivated the development of many decision support tools. This review shows that the tools differ in terms of the types of questions they can assist in answering. We identified three main groups: “How Much”-tools, “Where”-tools and “Which”-tools. The “How Much”-tools can further be grouped into tools quantifying hydraulic impacts, hydrologic impacts, water quality impacts, non-flow-related impacts and economic impacts. Additionally, the tools differ in terms of how many aspects of water they address, from those focused only on bio-physical aspects to those attempting to find the best WSUD based on multiple criteria. Finally, we suggest that variability among the tools can partly be explained by variability in local context including conditions such as type of existing stormwater systems, groundwater conditions and legislative frameworks

Heregulin drives endocrine resistance by altering il-8 expression in er-positive breast cancer

Sustained HER2/HER3 signaling due to the overproduction of the HER3 ligand heregulin (HRG) is proposed as a key contributor to endocrine resistance in estrogen receptor-positive (ER+) breast cancer. The molecular mechanisms linking HER2 transactivation by HRG-bound HER3 to the acquisition of a hormone-independent phenotype in ER+ breast cancer is, however, largely unknown. Here, we explored the possibility that autocrine HRG signaling drives cytokine-related endocrine resistance in ER+ breast cancer cells. We used human cytokine antibody arrays to semi-quantitatively measure the expression level of 60 cytokines and growth factors in the extracellular milieu of MCF-7 cells engineered to overexpress full-length HRGβ2 (MCF-7/HRG cells). Interleukin-8 (IL-8), a chemokine closely linked to ER inaction, emerged as one the most differentially expressed cytokines. Cytokine profiling using structural deletion mutants lacking both the N-terminus and the cytoplasmic-transmembrane region of HRGβ2—which is not secreted and cannot transactivate HER2—or lacking a nuclear localization signal at the N-terminus—which cannot localize at the nucleus but is actively secreted and transactivates HER2—revealed that the HRG-driven activation of IL-8 expression in ER+ cells required HRG secretion and transactivation of HER2 but not HRG nuclear localization. The functional blockade of IL-8 with a specific antibody inversely regulated ERα-driven transcriptional activation in endocrine-sensitive MCF-7 cells and endocrine-resistant MCF-7/HRG cells. Overall, these findings suggest that IL-8 participates in the HRG-driven endocrine resistance program in ER+/HER2- breast cancer and might illuminate a potential clinical setting for IL8- or CXCR1/2-neutralizing antibodies.Fil: Papadimitropoulou, Adriana. Academy of Athens; GreciaFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Atlas, Ella. University of Ottawa; CanadáFil: Steen, Travis Vander. Mayo Clinic; Estados UnidosFil: Cuyàs, Elisabet. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; España. Institut Català d'Oncologia; EspañaFil: Verdura, Sara. Institut Català d'Oncologia; España. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; EspañaFil: Espinoza, Ingrid. University of Mississippi; Estados UnidosFil: Menendez, Javier A.. Institut Català d'Oncologia; España. Institut D'investigació Biomèdica de Girona Dr. Josep Trueta; EspañaFil: Lupu, Ruth. Mayo Clinic; Estados Unidos. University of Ottawa; Canadá. Mayo Clinic Cancer Center; Estados Unido