PopWiss - Datenbank der Populärwissenschaft. Lessons learned - Herausforderungen der Informationsintegration in einem interdisziplinären Forschungsprojekt

Das Projekt PopWiss hat das Ziel, ein Informationssystem für populäre Wissenschaftskommunikation aufzubauen. Populäre Wissenschaft wird zunehmend von der Wissenschaftskommunikation durch Forschende selbst geprägt. Neben traditionelle Formate wie dem populärwissenschaftlichen Vortrag, dem populären Sachbuch, dem Gastbeitrag in Zeitschriften oder Zeitungen treten im Internetumfeld neue Formate, die es Forschenden gestatten, ihre Wissenschaft in Eigenregie zu vermitteln und direkt mit Zielgruppen außerhalb ihrer jeweiligen Scientific Community in Dialoge zu treten. Hierzu zählen Blogs, dazu Videos, Themenportale, Newsletter, MOOCs usw. Zudem entstanden vielfältige neue Offline-Formate wie Kinderuni, Science Slam oder Lange Nacht der Wissenschaft. Die PopWiss-Datenbank soll eine Übersicht ermöglichen, welche Forschenden wie häufig welche Formate der Wissenschaftskommunikation bedienen. Bei der Entwicklung sind folgende Zielgruppen im Fokus: Berufungskommissionen (welche perspektivisch auch die Leistungen von Bewerbern in externer Wissenschaftskommunikation erheben und miteinander vergleichen) sowie die Organisatoren populärwissenschaftlicher Veranstaltungen, die geeignete Personen suchen, z. B. Journalisten. PopWiss soll eine Basis für Qualitätskriterien für entsprechendes Engagement bilden, um langfristig Exzellenz in Wissenschaftskommunikation für eine Karriere in der Wissenschaft anrechenbar zu machen. Neben den komplexen inhaltlichen Fragestellungen sind es Aspekte der Datenqualität, Erschließung, Metadatenstrukturierung und Fragen der Authentifizierung und Autorisierung, die im Projekt vorrangig von der KIT-Bibliothek bearbeitet werden. Das Projekt wird von der Tschira-Stiftung gefördert und vom Nationalen Institut für Wissenschaftskommunikation (NaWiK), der KIT-Bibliothek und dem Institut für Angewandte Informatik am KIT durchgeführt

Genetic variations in bile acid homeostasis are not overrepresented in alcoholic cirrhosis compared to patients with heavy alcohol abuse and absent liver disease

Increased serum bile salt levels have been associated to a single-nucleotide polymorphism in the bile salt export pump (BSEP; ABCB11) in several acquired cholestatic liver diseases but there is little evidence in alcoholic liver disease (ALD). Furthermore, a crosstalk between vitamin D and bile acid synthesis has recently been discovered. Whether this crosstalk has an influence on the course of ALD is unclear to date. Our aim was to analyse the role of genetic polymorphisms in BSEP and the vitamin D receptor gene (NR1I1) on the emergence of cirrhosis in patients with ALD. Therefore, 511 alcoholic patients (131 with cirrhosis and 380 without cirrhosis) underwent ABCB11 genotyping (rs2287622). Of these, 321 (131 with cirrhosis and 190 without cirrhosis) were also tested for NR1I1 polymorphisms (bat-haplotype: BsmI rs1544410, ApaI rs7975232 and TaqI rs731236). Frequencies of ABCB11 and NR1I1 genotypes and haplotypes were compared between alcoholic patients with and without cirrhosis and correlated to serum bile salt, bilirubin and aspartate aminotransferase levels in those with cirrhosis. Frequencies of ABCB11 and NR1I1 genotypes and haplotypes did not differ between the two subgroups and no significant association between genotypes/haplotypes and liver function tests could be determined for neither polymorphism. We conclude that ABCB11 and NR1I1 polymorphisms are obviously not associated with development of cirrhosis in patients with AL

Disturbed eating at high altitude: influence of food preferences, acute mountain sickness and satiation hormones

Purpose: Hypoxia has been shown to reduce energy intake and lead to weight loss, but the underlying mechanisms are unclear. The aim was therefore to assess changes in eating after rapid ascent to 4,559m and to investigate to what extent hypoxia, acute mountain sickness (AMS), food preferences and satiation hormones influence eating behavior. Methods: Participants (n=23) were studied at near sea level (Zurich (ZH), 446m) and on two days after rapid ascent to Capanna Margherita (MG) at 4,559m (MG2 and MG4). Changes in appetite, food preferences and energy intake in an ad libitum meal were assessed. Plasma concentrations of cholecystokinin, peptide tyrosine-tyrosine, gastrin, glucagon and amylin were measured. Peripheral oxygen saturation (SpO2) was monitored, and AMS assessed using the Lake Louis score. Results: Energy intake from the ad libitum meal was reduced on MG2 compared to ZH (643±308 vs. 952±458kcal, p=0.001), but was similar to ZH on MG4 (890±298kcal). Energy intake on all test days was correlated with hunger/satiety scores prior to the meal and AMS scores on MG2 but not with SpO2 on any of the 3days. Liking for high-fat foods before a meal predicted subsequent energy intake on all days. None of the satiation hormones showed significant differences between the 3days. Conclusion: Reduced energy intake after rapid ascent to high altitude is associated with AMS severity. This effect was not directly associated with hypoxia or changes in gastrointestinal hormones. Other peripheral and central factors appear to reduce food intake at high altitud

Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma

Background A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. Patients and methods Tumor samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=7) or short-term responding group (n=12) according to progression-free survival (PFS≥12 months vs. PFS<12 months). Next generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry. Results Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPS correlated with longer progression-free survival. PD-L1 positivity (CPS≥1) was further associated with an increased CD4+ memory T-cell score. The ERBB2 copy number as well as the tumor mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and co-amplifications in HER2 pathway associated genes such as EGFR, which were connected to trastuzumab resistance, were present in 10% of the patients and equally distributed between the groups. Conclusion The study highlights the clinical relevance of PD-L1 testing also in the context of trastuzumab treatment and offers a biological rational by demonstrating elevated CD4+ memory T-cells scores in the PD-L1-positive group

Downregulation of duodenal SLC transporters and activation of proinflammatory signaling constitute the early response to high altitude in humans

Solute carrier (SLC) transporters mediate the uptake of biologically active compounds in the intestine. Reduced oxygenation (hypoxia) is an important factor influencing intestinal homeostasis. The aim of this study was to investigate the pathophysiological consequences of hypoxia on the expression and function of SLCs in human intestine. Hypoxia was induced in human intestinal epithelial cells (IECs) in vitro (0.2; 1% O2 or CoCl2). For human in vivo studies, duodenal biopsies and serum samples were obtained from individuals (n = 16) acutely exposed to 4,554 meters above sea levels. Expression of relevant targets was analyzed by quantitative PCR, Western blotting, or immunofluorescence. Serum levels of inflammatory mediators and nucleosides were determined by ELISA and LC/MS-MS, respectively. In the duodenum of volunteers exposed to high altitude we observed decreased mRNA levels of apical sodium-dependent bile acid transporter (ASBT), concentrative nucleoside transporters 1/2 (CNT1/2), organic anion transporting polypeptide 2B1 (OATP2B1), organic cation transporter 2 (OCTN2), peptide transporter 1 (PEPT1), serotonin transporter (SERT), and higher levels of IFN-γ, IL-6, and IL-17A. Serum levels of IL-10, IFN-γ, matrix metalloproteinase-2 (MMP-2), and serotonin were elevated, whereas the levels of uridine decreased upon exposure to hypoxia. Hypoxic IECs showed reduced levels of equilibrative nucleoside transporter 2 (ENT2), OCTN2, and SERT mRNAs in vitro, which was confirmed on the protein level and was accompanied by activation of ERK1/2, increase of hypoxia-inducible factor (HIF) proteins, and production of IL-8 mRNA. Costimulation with IFN-γ and IL-6 during hypoxia further decreased the expression of SERT, ENT2, and CNT2 in vitro. Reduced oxygen supply affects the expression pattern of duodenal SLCs that is accompanied by changes in serum levels of proinflammatory cytokines and biologically active compounds demonstrating that intestinal transport is affected during systemic exposure to hypoxia in humans

Разработка магнитной оправки для алмазного выглаживания

Объектом исследования является магнитная оправка. Актуальность разработки оправки для алмазного выглаживания заключается в том, что в процессе выглаживания требуется стабильное усилие выглаживания независимо от неточности геометрической формы детали и погрешностей установки. Целью данной выпускной квалификационной работы является разработка оправки для алмазного выглаживания, которая не имеет пару трения и позволяет проводить выглаживание с маленьким колебанием усилия выглаживания. Рассматриваемые вопросы: как проводить алмазное выглаживание без силы трения, как регулировать усилия выглаживания для магнитной оправки и и т. д.The object of study is a magnetic mandrel. The relevance of the development of the mandrel for diamond smoothing is that the smoothing process requires a stable smoothing force, regardless of the inaccuracy of the geometric shape of the part and the installation errors. The purpose of this final qualifying work is to develop a mandrel for diamond smoothing, which does not have a friction pair and allows smoothing with a small fluctuation in the effort of smoothing. Questions to be addressed: how to carry out diamond smoothing without friction, how to adjust the smoothing efforts for a magnetic mandrel and etc

Strukturrevision einer weit verbreiteten marinen Sulfonolipidklasse basierend auf deren Isolierung und Totalsynthese

Bakterien der marinen Roseobacter-Gruppe spielen eine wichtige Rolle in globalen biogeochemischen Prozessen. Prominente Vetreter dieser Gruppe produzieren schwefelhaltige Aminolipide (SAL), die für die Bildung von Biofilmen und die Besiedlung von Meeresoberflächen von entscheidender Bedeutung sind. Obwohl Genome Mining-Ansätze und massenspektrometrische Studien homotaurinhaltige Strukturen für eine Gruppe von SALs postulierten, blieben deren relative und absolute Strukturen bisher unbekannt, was biochemische und funktionelle Untersuchungen behinderte. In dieser Studie konnten wir die absoluten Strukturen durch eine Kombination von analytischen Techniken, Isolierungs- und Abbauexperimenten sowie Totalsynthese bestimmen. Im Gegensatz zu vorherigen Strukturvorschlägen sind die hier untersuchten Aminolipide durch eine ungewöhnliche N,O-acylierte Cysteinolsäure Kopfgruppe gekennzeichnet, weshalb wir die Substanzklasse Cysteinolide genannt haben. Durch gezielte Netzwerk-basierende metabolomische Studien konnten wir zudem die Verteilung und strukturelle Vielfalt von Cysteinoliden in verschiedenee Vertretern der bakteriellen Roseobacter-Gruppe kartieren. Insgesamt konnten in dieser Studie 14 verschiedene Aminolipide, einschließlich der in dieser Studie isolierten Cysteinolide, synthetisiert werden. Der Vergleich der erhaltenen analytischen Daten ermöglichte tiefergehende strukturelle Einblicke in die Charakteristika diese Substanzgruppe, welche für Studien zum bakteriellen Sulfonolipid-Stoffwechsel und zu biogeochemischen Nährstoffkreislauf in den Ozeanen von großer Bedeutung sein werden

The corneal subbasal nerve plexus and thickness of the retinal layers in pediatric type 1 diabetes and matched controls

Optical coherence tomography (OCT) of the retina and corneal confocal laser scanning microscopy (CLSM) of the subbasal nerve plexus (SBP) are noninvasive techniques for quantification of the ocular neurodegenerative changes in individuals with type 1 diabetes mellitus (T1DM). In adult T1DM patients these changes are hardly related to T1DM only. Instead, ageing and/or lifestyle associated comorbidities have to be considered as putative confounding variables. Therefore, we investigated pediatric T1DM patients (n = 28; 14.2 ± 2.51 y; duration of disease: 5.39 ± 4.16 y) without clinical signs of diabetic retina disease, neuropathy, vasculopathy or nephropathy and compared our findings with those obtained in healthy controls (n = 46; 14.8 ± 1.89 y). The SBP was characterized by the averaged length, thickness, and tortuosity of nerve fibers as well as the number of branching and connecting points. OCT was used to determine the total thickness of the retina (ALL) and the thickness of each retinal layer. Both methods revealed signs of early neurodegenerative changes, e.g. thinning of distinct retinal layers at the pericentral ring and shortening of corneal nerve fibers that are already present in pediatric T1DM patients. Standardization of instruments and algorithms are urgently required to enable uniform comparison between different groups and define normative values to introduce in the clinical setting

Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity

Summary Adoptive transfer of T cells genetically modified with tumour-specific T-cell receptors (TCR) is a promising novel approach in the treatment of cancer. We have previously isolated an allorestricted MHC class I-restricted TCR with specificity for Formin-like protein 1 (FMNL1) with potent activity against chronic lymphocytic leukaemia cells. CD4 + T cells have been described to be highly important for tumour elimination although TCR derived from CD4 + T cells with anti-tumour reactivity have been only rarely described. In this study we aimed to isolate MHC class-II-restricted CD4 + T cells and TCR with specificity for leukaemia antigens. We used professional antigen-presenting cells pulsed with the leukaemiaassociated and tumour-associated antigen FMNL1 for stimulation of autologous T cells in vitro. We isolated two CD4 + HLA-DR-restricted T-cell clones and T-cell-derived TCR with so far unknown specificity but high reactivity against lymphoma cells and native malignant cells derived from HLA-matched patients with diverse leukaemias. Moreover, characterization of the TCR after TCR gene transfer revealed that specific characteristics of isolated TCR as reactivity in response to Toll-like receptors were transferable on effector cells. Our results have a major impact on the development of novel immunotherapies. They demonstrate that TCR with potent HLA-DR-restricted anti-leukaemic reactivity against so far undefined self-restricted antigens can be isolated from the healthy autorestricted CD4 + T-cell repertoire and these TCR are highly interesting candidate tools for novel immunotherapies