Functional analysis of the transcription factors Sp3 and Sp4

Biological processes are largely controlled by the synthesis and the modulation of proteins. For the synthesis of proteins. two steps are of critical importance. Firstly, the genetic information for the protein has to be transcribed from the DNA of the gene encoding the protein to the mRNA intermediate and secondly the mRNA has to be translated into the amino acid sequence that forms the protein

Kopersmotieven Bastioneiland Leeuwarden:duurzame woningen? Of toch de fantastische natuur

Voor vaststelling van ons doel hebben we rekening gehouden met de probleemstelling die in dit rapport centraal staat: ‘Wat zijn de kopersmotieven van de bewoners van Bastioneiland?’ Als onderzoeksdoel hebben we dan ook gekozen voor de volgende verwoording: “Inzicht verkrijgen in de verschillende motieven die een rol hebben gespeeld bij de koop van een woning op Bastioneiland voor de huidige bewoners.” Het praktijkdoel is als het ware het hogere doel van ons onderzoek. Deze luidt dan ook: “Het in kaart brengen van de kopersmotieven van de bewoners zodat deze gebruikt kunnen worden voor volgende projecten”. Door te onderzoeken welke aspecten voor de bewoners het meest doorslaggevend zijn geweest, kan een beeld gecreëerd worden van de wensen van potentiële toekomstige kopers van een ander (vergelijkbaar) project. Zo kan er in de toekomst gebruik worden gemaakt van onze bevindingen en op deze manier kan een project meer succesvol worden gemaakt. Studentenonderzoek in het kader van het thema Duurzaam bouwe

A Land System representation for global assessments and land-use modeling

Current global scale land-change models used for integrated assessments and climate modeling are based on classifications of land cover. However, land-use management intensity and livestock keeping are also important aspects of land use, and are an integrated part of land systems. This article aims to classify, map, and to characterize Land Systems (LS) at a global scale and analyze the spatial determinants of these systems. Besides proposing such a classification, the article tests if global assessments can be based on globally uniform allocation rules. Land cover, livestock, and agricultural intensity data are used to map LS using a hierarchical classification method. Logistic regressions are used to analyze variation in spatial determinants of LS. The analysis of the spatial determinants of LS indicates strong associations between LS and a range of socioeconomic and biophysical indicators of human-environment interactions. The set of identified spatial determinants of a LS differs among regions and scales, especially for (mosaic) cropland systems, grassland systems with livestock, and settlements. (Semi-)Natural LS have more similar spatial determinants across regions and scales. Using LS in global models is expected to result in a more accurate representation of land use capturing important aspects of land systems and land architecture: the variation in land cover and the link between land-use intensity and landscape composition. Because the set of most important spatial determinants of LS varies among regions and scales, land-change models that include the human drivers of land change are best parameterized at sub-global level, where similar biophysical, socioeconomic and cultural conditions prevail in the specific regions. © 2012 Blackwell Publishing Ltd

Exploring wastewater nitrogen and phosphorus flows in urban and rural areas in China for the period 1970 to 2015

China has experienced rapid population growth and increasing human N and P discharge from point sources. This paper presents a new spatial and temporal model-based, province-scale inventory of N and P in wastewater using detailed information on the location and functioning of 4436 WWTPs covering China for the period 1970–2015. China's nutrient discharge to surface water increased 22-fold from 177 to 3908 Gg N yr−1 and 29-fold from 20 to 577 Gg P yr−1 in urban areas between 1970 and 2015. The ten strongly urbanized and industrialized provinces along the Eastern coast contributed 43 % of China's total N and P discharge to surface water in 2015. At present, the contribution of rural areas to total wastewater discharge (2082 Gg N yr−1 and 434 Gg P yr−1) is 35 % for N and 43 % for P. The model approach and sensitivity analysis of this study indicate that policies aiming at improving water quality need to consider these regional differences, i.e., improvement of the wastewater treatment technology level in Eastern regions and increasing both the sewage connection and wastewater treatment in Central and Western regions

Integrating Life Cycle and Impact Assessments to Map Food's Cumulative Environmental Footprint

Producing food exerts pressures on the environment. Understanding the location and magnitude of food production is key to reducing the impacts of these pressures on nature and people. In this Perspective, Kuempel et al. outline an approach for integrating life cycle assessment and cumulative impact mapping data and methodologies to map the cumulative environmental pressure of food systems. The approach enables quantification of current and potential future environmental pressures, which are needed to reduce the net impact of feeding humanity. © 2020 The AuthorsFeeding a growing, increasingly affluent population while limiting environmental pressures of food production is a central challenge for society. Understanding the location and magnitude of food production is key to addressing this challenge because pressures vary substantially across food production types. Applying data and models from life cycle assessment with the methodologies for mapping cumulative environmental impacts of human activities (hereafter cumulative impact mapping) provides a powerful approach to spatially map the cumulative environmental pressure of food production in a way that is consistent and comprehensive across food types. However, these methodologies have yet to be combined. By synthesizing life cycle assessment and cumulative impact mapping methodologies, we provide guidance for comprehensively and cumulatively mapping the environmental pressures (e.g., greenhouse gas emissions, spatial occupancy, and freshwater use) associated with food production systems. This spatial approach enables quantification of current and potential future environmental pressures, which is needed for decision makers to create more sustainable food policies and practices. © 2020 The Author

Clinical utility of FDG PET in Parkinson\u2019s disease and atypical parkinsonism associated with dementia

Purpose: There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson\u2019s disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. Methods: We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. Results: Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. Conclusion: Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC

Experience in South Africa of combining bioanalysis and instrumental analysis of PCDD/Fs

We outline the experiences and the challenges of optimizing two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOF-MS) in conjunction with the H4IIE-luc bioassay for analyzing polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the South African context. Investigating such alternative analytical methods can assist countries with developing economies to meet their obligations under the Stockholm Convention.Water Research Commission (WRC) of South Africa (K5/1561) and the South African/Norwegian Bilateral Agreement administered by the National Research Foundations (NRF) of South Africa and the Research Council of Norway (UID 64489).The authors also acknowledge support from a Discovery Grant from the National Science and Engineering Research Council of Canada (Project # 326415-07) and an instrumentation grant from the Canada Foundation for Infrastructure. Prof. Giesy was supported by the program of 2012 "High Level Foreign Experts" (#GDW20123200120) funded by the State Administration of Foreign Experts Affairs,the P.R. China to Nanjing University and the Einstein Professor Program of the Chinese Academy of Sciences. He was also supported by the Canada Research Chair program, an at large Chair Professorship at the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong.http://www.elsevier.com/locate/trachb201