Pledge for a transformative science : a conceptual framework

"Transformative science" is a concept that delineates the new role of science for knowledge societies in the age of reflexive modernity. The paper develops the program of a transformative science, which goes beyond observing and analyzing societal transformations, but rather takes an active role in initiating and catalyzing change processes. The aim of transformative science is to achieve a deeper understanding of ongoing transformations and increased societal capacity for reflexivity with regard to these fundamental change processes. The concept of transformative science is grounded in an experimental paradigm, which has implications for (1) research, (2) education and learning, and (3) institutional structures and change in the science system. The article develops the theoretical foundations of the concept of transformative science and spells out the concrete implications in these three dimensions

Pledge for a transformative science: a conceptual framework

"Transformative science" is a concept that delineates the new role of science for knowledge societies in the age of reflexive modernity. The paper develops the program of a transformative science, which goes beyond observing and analyzing societal transformations, but rather takes an active role in initiating and catalyzing change processes. The aim of transformative science is to achieve a deeper understanding of ongoing transformations and increased societal capacity for reflexivity with regard to these fundamental change processes. The concept of transformative science is grounded in an experimental paradigm, which has implications for (1) research, (2) education and learning, and (3) institutional structures and change in the science system. The article develops the theoretical foundations of the concept of transformative science and spells out the concrete implications in these three dimensions

Transformative Forschung als Motor für die Gestaltung von Systemübergängen

Die „große Transformation“ hat eine lange unterschätzte innovations- und wissenschaftspolitische Dimension. Diese Dimension hat im Wissenschaftsjahr 2012 erheblich an Kontur gewonnen

Three-dimensional pathological size assessment in primary breast carcinoma

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P=0.0003, TV: P=0.0009, TSA: P<0.0001; multivariate analyses: MD: P=0.0018, TV: P=0.0109, TSA: P=0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alon

High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma

Purpose: Ovarian carcinoma in most instances is diagnosed in an advanced stage which cannot be cured by surgical tumor debulking alone. Standard adjuvant chemotherapy usually follows surgical procedures. Yet, few reliable predictive tissue markers exist for the response of ovarian carcinoma to chemotherapy. In this study, we evaluated the predictive value of IL-17- and FOXP3-positive tumor immune cell infiltration (TICI) for response to chemotherapy in ovarian carcinoma. Methods: Formalin fixed and paraffin embedded biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were immunostained with IL-17 and FOXP3 on a tissue microarray. Chemoresistance was defined as tumor recurrence within 6months of the completion of platinum-based chemotherapy. In 94 and 90 biopsies, conclusive data for IL-17 and FOXP3 were available, respectively. Results: IL-17, but not FOXP3-positive TICI, displayed a significantly higher density in biopsies of chemosensitive tumors (p=0.01). No significant difference in the expression of IL-17 and FOXP3 TICI was observed in all paired primary and recurrent biopsies without respect to chemoresponse (p=0.77 and p=0.87, respectively). However, significantly more IL-17-positive recurrences were encountered in the group of patients with chemosensitive tumors (p=0.008). Conclusions: High IL-17-positive TICI is indicative for response to chemotherapy in ovarian carcinoma. Higher frequency of IL-17-positive TICI might persist in recurrent tumor tissues of chemosensitive biopsies, suggesting repetitive platinum-based chemotherapy as an appropriate therapy for patients with IL-17-positive recurrence

Non-target screening with high-resolution mass spectrometry: critical review using a collaborative trial on water analysis

In this article, a dataset from a collaborative nontarget screening trial organised by the NORMAN Association is used to review the state-of-the-art and discuss future perspectives of non-target screening using high-resolution mass spectrometry in water analysis. A total of 18 institutes from 12 European countries analysed an extract of the same water sample collected from the River Danube with either one or both of liquid and gas chromatography coupled with mass spectrometry detection. This article focuses mainly on the use of high resolution screening techniques with target, suspect, and non-target workflows to identify substances in environmental samples. Specific examples are given to emphasise major challenges including isobaric and co-eluting substances, dependence on target and suspect lists, formula assignment, the use of retention information, and the confidence of identification. Approaches and methods applicable to unit resolution data are also discussed. Although most substances were identified using high resolution data with target and suspect-screening approaches, some participants proposed tentative non-target identifications. This comprehensive dataset revealed that nontarget analytical techniques are already substantially harmonised between the participants, but the data processing remains time-consuming. Although the objective of a Bfullyautomated identification workflow^ remains elusive in the short term, important steps in this direction have been taken, exemplified by the growing popularity of suspect screening approaches. Major recommendations to improve non-target screening include better integration and connection of desired features into software packages, the exchange of target and suspect lists, and the contribution of more spectra from standard substances into (openly accessible) databases.This work was supported in part by the SOLUTIONS project, which received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant Agreement No. 603437

Adhesion Class GPCRs (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [8] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [82, 332]. Several receptors have been suggested to function as mechanosensors [254, 234, 315, 32]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [100]

Adhesion Class GPCRs in GtoPdb v.2023.1

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [10] containing a GPCR proteolysis site (GPS). The N-terminal extracellular region often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [104, 418]. Several receptors have been suggested to function as mechanosensors [320, 288, 396, 38]. Cryo-EM structures of the 7-transmembrane domain of several adhesion GPCRs have been determined recently [292, 21, 403, 212, 300, 302, 431, 293]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [125]

Adhesion Class GPCRs in GtoPdb v.2021.3

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [9] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [101, 403]. Several receptors have been suggested to function as mechanosensors [309, 280, 383, 35]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [122]