Design and marketing: Intersections and challenges

This editorial article reports on interdisciplinary research being conducted at the interface between the scientific disciplines of marketing and design. It reviews the 11 academic papers from the special issue situated at this intersection, thereby showing the richness of research happening in this liminal area. At the same time, the paper observes how the disciplines' different scopes as well as their different modi operandi inhibit the collaboration between marketing and design research. Whereas marketing largely follows the paradigm of empirical realism asking how the current world works, design largely follows the pragmatist paradigm asking how a future world can be shaped. Finally, this paper contains a number of suggestions on how to foster cooperation between the two disciplines.FCT:UIDB/04020/2020info:eu-repo/semantics/publishedVersio

The interplay of marketing and design

This paper provides insights into the interdisciplinary intersections between marketing and design. It explores the various design intersections in the marketing fields. The collaboration between marketing and design is restricted by the paradigm boundaries, but not by the industry, researchers, and research projects. Challenges for both disciplines' future are explored, highlighting the need for a paradigm shift in marketing.FCT: UIDB/04020/2020info:eu-repo/semantics/publishedVersio

Combining heterogeneous subgroups with graph-structured variable selection priors for Cox regression

Important objectives in cancer research are the prediction of a patient's risk based on molecular measurements such as gene expression data and the identification of new prognostic biomarkers (e.g. genes). In clinical practice, this is often challenging because patient cohorts are typically small and can be heterogeneous. In classical subgroup analysis, a separate prediction model is fitted using only the data of one specific cohort. However, this can lead to a loss of power when the sample size is small. Simple pooling of all cohorts, on the other hand, can lead to biased results, especially when the cohorts are heterogeneous. For this situation, we propose a new Bayesian approach suitable for continuous molecular measurements and survival outcome that identifies the important predictors and provides a separate risk prediction model for each cohort. It allows sharing information between cohorts to increase power by assuming a graph linking predictors within and across different cohorts. The graph helps to identify pathways of functionally related genes and genes that are simultaneously prognostic in different cohorts. Results demonstrate that our proposed approach is superior to the standard approaches in terms of prediction performance and increased power in variable selection when the sample size is small.Comment: under review, 19 pages, 10 figure

Mutations in a Novel, Cryptic Exon of the Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene Cause Male Pseudohermaphroditism

Joerg Gromoll and colleagues describe the identification and characterization of a novel exon that appears to be a new regulatory element within the luteinizing hormone/chorionic gonadotropin receptor gene of three individuals with Leydig cell hypoplasia

Forschungsbericht zur Ist-Stands-Analyse im BMBF Verbundvorhaben ChemNet

Der vorliegende Forschungsbericht ist das erste Teilergebnis der wissenschaftlichen Begleitforschung im vom BMBF geförderten Projekt ChemNet. Mit ChemNet soll eine Online-Plattform entwickelt werden die für die Erstausbildung, die berufliche Weiterbildung als auch für die Aufstiegsqualifizierung im Chemiesektor genutzt werden kann – dies sogar im europäischen Kontext. Der Forschungsbericht stellt die Ergebnisse der Ist-Stand-Analyse von u.a. Ausbildungsverhältnissen, Computernutzung und Computerbezogenen Einstellungen von Auszubildenden, Teilnehmern der Aufstiegsqualifizierung, Berufsschullehrern, Ausbildern in der überbetrieblichen Ausbildung sowie betrieblichen Ausbildern dar. Dabei wurden etablierte Instrumente aus dem Inventar zur Computerbildung (INCOBI-R) verwendet. Deutlich konnten dabei die Unterschiede in der Nutzung von Informations- und Kommunikationstechnologien zwischen den Gruppen von Lehrenden und Lernenden herausgearbeitet werden, die sich auch in den Computerbezogenen Einstellungen wiederspiegeln.:Abbildungsverzeichnis IV Tabellenverzeichnis IX 1 Einführung und Ausgangslage 1 2 Ziele und Design der Untersuchung 1 2.1 Problemhintergrund 1 2.2 Zielstellung 2 2.3 Zielgruppen 3 2.4 Theoretischer Hintergrund und Forschungsstand 3 2.4.1 Mediennutzung 3 2.4.2 Lernortkooperation 5 2.5 Forschungsdesign 8 2.5.1 Grundgesamtheit und Zahl der Rückläufe 9 2.5.2 Fragebogenkonstruktion 10 3 Präsentation der Daten 11 3.1 Soziodemografische Daten 12 3.1.1 Daten der Auszubildenden 12 3.1.2 Daten der Berufsschullehrer 15 3.1.3 Daten der Ausbilder der überbetrieblichen Bildungsstätte 17 3.1.4 Daten der betrieblichen Ausbilder 18 3.1.5 Daten der Teilnehmer der Aufstiegsqualifizierung zum Industriemeister 20 3.2 Berufliche Situation im Betrieb 22 3.2.1 Auszubildende 22 3.2.2 Betriebliche Ausbilder 27 3.2.3 Teilnehmer der Aufstiegsqualifizierung 29 3.3 Ausbildungssituation an ÜBS und Berufsschule 33 3.4 Einschätzung des Ausbildungsstandes 34 3.4.1 Selbsteinschätzung der Auszubildenden 34 3.4.2 Fremdeinschätzung durch Berufsschullehrer und (über-)betriebliche Ausbilder 36 3.4.3 Selbsteinschätzung der Teilnehmer der Aufstiegsqualifizierung 43 3.5 Kommunikation 46 3.5.1 Fachlicher Austausch 46 3.5.2 Kommunikationswege/-mittel 49 3.5.3 Einschätzung der Kommunikation 58 3.6 Mediennutzung 66 3.6.1 Computernutzung 66 3.6.2 Internetnutzung 79 3.6.3 Sicherheit im Umgang mit Computern und Computeranwendungen 91 3.6.4 Computerbezogene Einstellungen 97 4 Weiterführende Analyse der Daten 107 4.1 Mittelwertdarstellungen von Alter, Ausbildertätigkeit und Computernutzung in Jahren 107 4.2 Vergleich der Gruppenvarianzen – einfaktorielle ANOVA 108 5 Zusammenfassung und weitere Arbeitsschritte 110 5.1 Zusammenfassung 110 5.2 Weitere Arbeitsschritte 112 6 Quellen 11

Exceptional Response to Pembrolizumab in a Mismatch Repair-Deficient Aggressive Prostate Cancer with Somatic EPCAM, MSH2, and MSH6 Co-Deletion: A Case Report.

Mismatch repair-deficient (dMMR) prostate cancer (PCa) is a rare (1-5%) but highly actionable molecular subgroup of PCa, vulnerable to immune checkpoint inhibitors. Our case of sporadic dMMR PCa due to large monoallelic co-deletion of EPCAM, MSH2, and MSH6 features a clinically aggressive disease presentation and a major response to pembrolizumab. We report a 65-year-old patient with primary metastatic PCa, Gleason score 5 + 5 = 10, with penile and lymph node metastases at diagnosis. Patient showed rapid progression on first-line ADT and enzalutamide. Tumor next-generation sequencing (NGS) revealed microsatellite instability and a tumor mutational burden of 40.8 mutations/megabase. Immunohistochemistry showed co-loss of MSH2 and MSH6. Review of NGS row data confirmed large monoallelic deletion in chromosome 2p, including EPCAM, MSH2, and MSH6. No germline alterations in mismatch repair genes were detected. Patient showed excellent response to pembrolizumab, which is still ongoing. We conclude that early molecular tumor profiling is essential to enable personalized management of advanced PCa, especially in patients with aggressive or atypical disease course

Probe dependence of allosteric enhancers on the binding affinity of adenosine A1‐receptor agonists at rat and human A1‐receptors measured using NanoBRET

Background and Purpose: Adenosine is a local mediator that regulates a number of physiological and pathological processes via activation of adenosine A1‐receptors. The activity of adenosine can be regulated at the level of its target receptor via drugs that bind to an allosteric site on the A1‐receptor. Here, we have investigated the species and probe dependence of two allosteric modulators on the binding characteristics of fluorescent and nonfluorescent A1‐receptor agonists. Experimental Approach: A Nano‐luciferase (Nluc) BRET (NanoBRET) methodology was used. This used N‐terminal Nluc‐tagged A1‐receptors expressed in HEK293T cells in conjunction with both fluorescent A1‐receptor agonists (adenosine and NECA analogues) and a fluorescent antagonist CA200645.Key Results: PD 81,723 and VCP171 elicited positive allosteric effects on the binding affinity of orthosteric agonists at both the rat and human A1‐receptors that showed clear probe dependence. Thus, the allosteric effect on the highly selective partial agonist capadenoson was much less marked than for the full agonists NECA, adenosine, and CCPA in both species. VCP171 and, to a lesser extent, PD 81,723, also increased the specific binding of three fluorescent A1‐receptor agonists in a species‐dependent manner that involved increases in Bmax and pKD.Conclusions and Implications: These results demonstrate the power of the NanoBRET ligand‐binding approach to study the effect of allosteric ligands on the binding of fluorescent agonists to the adenosine A1‐receptor in intact living cells. Furthermore, our studies suggest that VCP171 and PD 81,723 may switch a proportion of A1‐receptors to an active agonist conformation (R*)

Improvement of pain experience and changes in heart rate variability through music-imaginative pain treatment

Music-imaginative Pain Treatment (MIPT) is a form of music therapy addressing pain experience and affective attitudes toward pain. It includes two self-composed music pieces: one dedicated to the pain experience (pain music, PM) and the other to healing imagination (healing music, HM). Our non-experimental study addresses patients with chronic somatoform pain disorders participating in MIPT. The goal is to gain insight into the direct effect mechanisms of MIPT by combining outcome measures on both the objective physiological and subjective perception levels. The research questions are directed toward changes in pain experience and heart rate variability and their correlations. Thirty-seven hospitalized patients with chronic or somatoform pain disorders receiving MIPT participated in this study. Demographic data and psychometric measures (Symptom Check List SCL90, Childhood Trauma Questionnaire CTQ) were collected to characterize the sample. Subjective pain experience was measured by McGill Pain Questionnaire (SF-MPQ), and Heart Rate Variability by 24 h-ECG. Data analysis shows a reduction of reported pain from MT1 = 19.1 (SD = 7.3) to MT2 = 10.6 (SD = 8.0) in all dimensions of the SF-MPQ. HRV analyses shows a reduced absolute power during PM and HM, while a relative shift in the autonomic system toward higher vagal activity appears during HM. Significant correlations between HRV and MPQ could not be calculated. Findings are interpreted as a physiological correlate to the psychological processes of the patients. Future studies with more participants, a control-group design, and the integration of medium- and long-term effects are recommended

Biofunctionalization of annealed nanodiamonds

In the last decades nanodiamonds have received special attention from the scientific community as a new carbon material with unique properties. Along with the macrosize diamond, those nanoparticles exhibit an exceptional hardness and sp3-core whereas, the size allows different applications. Among others they can be applied in new composites, lubrication oils, polishing and electronic materials, and drug delivery, biolabeling and bioimaging systems. To improve biocompatibility of diamond nanocrystals the surface functionalization is a favorable solution. The nanodiamonds the authors used were obtained by detonation synthesis and for this possess several functional groups on the surface. Further modifications require a homogeneous surface. In this approach a thermal methodology was used to remove the functional groups in order to produce an uniform carbon surface. The chosen biomolecules were phenylalanine, glutathione, biotin and O-phosphorylethanolamine to increase the biological suitability. The thermal annealing process was performed at three different temperatures: 750 °C, 900 °C and 1100 °C, under nitrogen flow to prevent oxidation. In the end of the procedure, samples were characterized by infrared spectroscopy, thermogravimetric analysis and transmission electron microscopy. The results revealed a significant decrease in functional groups for all temperatures. At 1100 °C onion like carbon can be identified in our sample, proving of a successful graphitization of the nanodiamonds. For biofunctionalization different approaches were applied: 1) carboxylation and further peptide bonding; 2) hydroxylation, silanization and further peptide bonding; 3) click chemistry, as depicted in figure 2. Success of the modification is verified by infrared spectroscopy and thermogravimetric analysis which evidence the success of the surface modification

CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis

Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.Fil: Blanco-Pérez, Frank. Paul-ehrlich-institut;Fil: Kato, Yoichiro. Tokyo Women's Medical University;Fil: Gonzalez-Menendez, Irene. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Laiño, Jonathan Emiliano. Paul-ehrlich-institut;Fil: Ohbayashi, Masaharu. Toyohashi Sozo University;Fil: Burggraf, Manja. Paul-ehrlich-institut;Fil: Krause, Maren. Paul-ehrlich-institut;Fil: Kirberg, Jörg. Paul-ehrlich-institut;Fil: Iwakura, Yoichiro. Tokyo University Of Science;Fil: Martella, Manuela. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Quintanilla-Martinez, Leticia. Universitätsklinikum Tübingen Medizinische Fakultät;Fil: Shibata, Noriyuki. Tokyo Women's Medical University;Fil: Vieths, Stefan. Paul-ehrlich-institut;Fil: Scheurer, Stephan. Paul-ehrlich-institut;Fil: Toda, Masako. Paul-ehrlich-institut; . Tohoku University