Transition Design Guide: Design für Nachhaltigkeit - Gestalten für das Heute und Morgen ; ein Guide für Gestaltung und Entwicklung in Unternehmen, Städten und Quartieren, Forschung und Lehre

Was hat Design mit Umwelt und Nachhaltigkeit zu tun? Die globale Erwärmung und der Klimawandel lassen sich auf verschiedene Ursachen zurückführen. Design, das die Umwelt außen vor lässt, ist einer der Gründe. Viele Produkte und Dienstleistungen verbrauchen nämlich viel Energie und Ressourcen haben auch eine hohe soziale Relevanz - sie sorgen beispielsweise für Teilhabe oder Exklusion. Wie eine Transformation hin zu mehr Nachhaltigkeit in diesem Bereich besser gelingt, fasst der neue "Transition Design Guide" des Wuppertal Instituts und der Folkwang Universität der Künste in Kooperation mit der ecosign - Akademie für Gestaltung Köln und der Bergischen Universität Wuppertal zusammen. Der Leitfaden gibt interessierten Gestaltenden, Entwickelnden, Transformatorinnen und Transformatoren sowie Forschenden in Universitäten, Unternehmen und Kommunen 16 Praxis-Werkzeuge an die Hand, um Produkte, Dienstleistungen, soziale Räume oder andere Erfahrungswelten nachhaltiger und umweltbewusster zu entwerfen. Anhand der Arbeitsblätter lassen sich gestalterische Ideen und Konzepte auf ihre Nachhaltigkeitspotenziale untersuchen und weiterentwickeln. Nachhaltigkeitsaspekte werden dabei mit den Methoden und Arbeitsschritten eines klassischen Designprozesses zusammengeführt. Ausführliche Hintergrundinformationen ergänzen die Themen der Tools inhaltlich. Anhang, Arbeitsblätter: https://epub.wupperinst.org/files/7567/WS55_2ed_Anhang.pd

Implementation of a National Reference Laboratory for Buruli Ulcer Disease in Togo

Background: In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Methodology: Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime'' and "Central,'' standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. Principal Findings: The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. Conclusions: High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory

Urban correction for the hydrological conditioning of the TanDEM-X DEM for the HydroSHEDS v2 database

The HydroSHEDS database provides global hydrographic data for hydrological applications. The second, refined version of the database is improved by using the highresolution TanDEM-X digital elevation model (DEM). In order to derive hydrologic data from the terrain, during the socalled pre-conditioning, the DEM is edited and ancillary layers are calculated. Prior steps of the editing include, among others like void and outlier correction and the derivation of a coastline and water body mask, an urban correction. When river networks are derived from a DEM, visible artificial structures can divert the streams as they intercept the natural course of the riverbed. Therefore, during the last step of the pre-conditioning, the urban correction aims to reduce such diversions caused by built-up structures

Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies

Large-scale compound screens are a powerful model system for understanding variability of treatment response and discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of the in vivo microenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture. Here, we established a high-throughput platform to measure ex vivo sensitivity of 108 primary blood cancer samples to 50 drugs in monoculture and coculture with bone marrow stromal cells. Stromal coculture conferred resistance to 52% of compounds in chronic lymphocytic leukemia (CLL) and 36% of compounds in acute myeloid leukemia (AML), including chemotherapeutics, B-cell receptor inhibitors, proteasome inhibitors, and Bromodomain and extraterminal domain inhibitors. Only the JAK inhibitors ruxolitinib and tofacitinib exhibited increased efficacy in AML and CLL stromal coculture. We further confirmed the importance of JAK-STAT signaling for stroma-mediated resistance by showing that stromal cells induce phosphorylation of STAT3 in CLL cells. We genetically characterized the 108 cancer samples and found that drug-gene associations strongly correlated between monoculture and coculture. However, effect sizes were lower in coculture, with more drug-gene associations detected in monoculture than in coculture. Our results justify a 2-step strategy for drug perturbation testing, with large-scale screening performed in monoculture, followed by focused evaluation of potential stroma-mediated resistances in coculture

The new hydrographic HydroSHEDS database derived from the TanDEM-X DEM

Water-related applications such as hydrology, hydrodynamics, and flood inundation modelling crucially require fundamental hydrographic knowledge and monitoring as well as the tools and data that support mapping and analysis of natural river and drainage characteristics. Since its introduction in 2008, HydroSHEDS is a well-established database providing seamless hydrographic information to support hydro-ecological research and applications on a multitude of scales by offering standardized spatial units for hydrological assessments. Although being widely used, the Shuttle Radar Topography Mission (SRTM)-based version 1 of HydroSHEDS has important limitations, in particular in areas above 60° N latitude. A steadily increasing availability and accuracy of remote sensing data promotes the development of a second and refined version of HydroSHEDS, which is based on the globally consistent and highly accurate TanDEM-X dataset. In light of this, HydroSHEDS v2 is currently created in collaboration between the German Aerospace Center (DLR), McGill University, Confluvio Consulting and the World Wildlife Fund. Within the HydroSHEDS workflow, the pre-conditioning comprises multiple editing and correction steps to prepare the TanDEM-X DEM for hydrological applications. Compared to HydroSHEDS v1, the resulting hydrologically conditioned DEM ensures a more accurate derivation of HydroSHEDS v2 core products such as flow directions, river courses and catchment boundaries. By providing even clearer and more complete views of Earth’s waterways, the HydroSHEDS geospatial framework serves various management and decisionmaking applications beyond scientific research including aquatic ecosystem services, human health impacts and conservation planning

Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL

The tumour microenvironment and genetic alterations collectively influence drug efficacy in cancer, but current evidence is limited and systematic analyses are lacking. Using chronic lymphocytic leukaemia (CLL) as a model disease, we investigated the influence of 17 microenvironmental stimuli on 12 drugs in 192 genetically characterised patient samples. Based on microenvironmental response, we identified four subgroups with distinct clinical outcomes beyond known prognostic markers. Response to multiple microenvironmental stimuli was amplified in trisomy 12 samples. Trisomy 12 was associated with a distinct epigenetic signature. Bromodomain inhibition reversed this epigenetic profile and could be used to target microenvironmental signalling in trisomy 12 CLL. We quantified the impact of microenvironmental stimuli on drug response and their dependence on genetic alterations, identifying interleukin 4 (IL4) and Toll-like receptor (TLR) stimulation as the strongest actuators of drug resistance. IL4 and TLR signalling activity was increased in CLL-infiltrated lymph nodes compared with healthy samples. High IL4 activity correlated with faster disease progression. The publicly available dataset can facilitate the investigation of cell-extrinsic mechanisms of drug resistance and disease progression

Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial

Ex vivo drug response profiling is a powerful tool to study genotype-drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers

Insight into the proteome of the hyperthermophilic Crenarchaeon Ignicoccus hospitalis: the major cytosolic and membrane proteins

Ignicoccus hospitalis, a hyperthermophilic, chemolithoautotrophic Crenarchaeon, is the host of Nanoarchaeum equitans. Together, they form an intimate association, the first among Archaea. Membranes are of fundamental importance for the interaction of I. hospitalis and N. equitans, as they harbour the proteins necessary for the transport of macromolecules like lipids, amino acids, and cofactors between these organisms. Here, we investigated the protein inventory of I. hospitalis cells, and were able to identify 20 proteins in total. Experimental evidence and predictions let us conclude that 11 are soluble cytosolic proteins, eight membrane or membrane-associated proteins, and a single one extracellular. The quantitatively dominating proteins in the cytoplasm (peroxiredoxin; thermosome) antagonize oxidative and temperature stress which I. hospitalis cells are exposed to at optimal growth conditions. Three abundant membrane protein complexes are found: the major protein of the outer membrane, which might protect the cell against the hostile environment, forms oligomeric complexes with pores of unknown selectivity; two other complexes of the cytoplasmic membrane, the hydrogenase and the ATP synthase, play a key role in energy production and conversion