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Andreas Monz leitet die Zentralabteilung in der Hessischen Staatskanzlei. Neben originären Verwaltungstätigkeiten werden dort wesentliche Themen der Staatsmodernisierung in Hessen inhaltlich gesteuert und für die Landesregierung aufbereitet. Andreas Monz ist Jurist und hat Verwaltungserfahrung von der kommunalen über die Landes- bis zur Bundesebene. Mehrere Jahre war er in koordinierender Funktion im politischen Bereich des Hessischen Landtags tätig. Er ist Fellow des Mercator Science-Policy Fellowship-Programms.
Vorwort: Dialogorientierte Wissenschaftskommunikation als Gewinn für Universitäten und Praxis
(2019)
Forschung und Lehre gelten als die Kernaufgaben deutscher Universitäten. In der öffentlichen Wahrnehmung von Universitäten spielt der ebenfalls in den Hochschulgesetzen der Länder festgeschriebene Transfer von wissenschaftlichen Erkenntnissen in Wirtschaft und Gesellschaft häufig eine untergeordnete Rolle, auch wenn Universitäten schon immer, beispielsweise durch Technologietransfer und Ausgründungen, wichtige Beiträge zur Wirtschaftsentwicklung leisten. ...
Nanoplastics (NP) and microplastics (MP) accumulate in our environment as a consequence of the massive consumption of plastics. Huge knowledge-gaps exist regarding uptake and fate of plastic particles in micro- and nano-dimensions in humans as well as on their impact on human health.
This study investigated the transport and effects of 50 nm and 0.5 μm COOH-modified polystyrene (PS) particles, as representatives for NP and MP, in different biological models in vitro. Acute toxicity and potential translocation of the particles were studied at the human intestinal and placental barrier using advanced in vitro co-culture models. Furthermore, embryotoxicity and genotoxicity were investigated as highly sensitive endpoints.
Polystyrene was not acutely toxic in both sizes (nano- and microparticles). No transport across the intestinal and placental barrier but a cellular uptake and intracellular accumulation of PS nano- and microparticles were determined. The particles were identified as weak embryotoxic and non-genotoxic.
In contrast to single-organ studies, this multi-endpoint study is providing a data-set with the exact same type of particles to compare organ-specific outcomes. Our study clearly shows the need to investigate other types of plastics as well as towards long-term or chronic effects of plastic particles in different biological models in vitro.
Since the financial crisis financial literacy has attracted growing interest among researchers and policy makers, as there is international empirical evidence that financial literacy is poor among both adults and students. In Germany we have almost no empirical evidence on financial literacy, especially in the case of students attending secondary schools, as financial education has not featured on German school curricula to date. Besides, Germany has not yet participated in the optional financial literacy module of PISA, which was offered for the first time in 2012. However, a lack of private pension provisioning, in spite of demographic change, and low stock ownership among German households indicate a deficit in financial knowledge and skills in this country as well.
In this paper we investigate financial literacy among students aged 14 to 16 attending a secondary school in the state of Hesse. The foundation is a test designed according to international standards. The statistical analysis of the test reveals substantial deficits in key areas of financial literacy. Particular deficits could be identified in the fields of basic knowledge of financial matters and, to an even greater degree, in more advanced concepts such as risk diversification. Applying interest calculations to financial matters turned out to be problematic for many students.
Furthermore, the paper analyses the impact of gender and type of school on the overall test score as well as test performance in specific tasks. The findings suggest that financial matters should be covered in some form at secondary schools. In light of the potentially far-reaching consequences of financial illiteracy for financial wellbeing, German participation in future PISA financial literacy tests seems highly advisable to gain a deeper understanding of the preliminary findings presented in this paper.
Uni-Highlights August 2019 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Uni-Highlights September 2019 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Revisiting the stealth trading hypothesis: does time-varying liquidity explain the size-effect?
(2019)
Large trades have a smaller price impact per share than medium-sized trades. So far, the literature has attributed this effect to the informational content of trades. In this paper, we show that this effect can arise from strategic order placement. We introduce the concept of a liquidity elasticity, measuring the responsiveness of liquidity demand with respect to changes in liquidity supply, as a major driver for a declining price impact per share. Empirical evidence based on Nasdaq stocks strongly supports theoretical predictions and shows that the aspect of liquidity coordination is an important complement to rationales based on asymmetric information.
Die Digitalisierung der Kommunikation: Gesellschaftliche Trends und der Wandel von Organisationen
(2019)
Die Publikation bieten einen Überblick zu den mit der Digitalisierung der Kommunikation zusammenhängenden gesellschaftlichen Trends wie Always-On Kultur, Shitstorm, Fake News und den Auswirkungen auf Schulen, Medien, Nichtregierungsorganisationen, Arbeitswelt und Sport.
Diese Publikation liegt auch als Science Policy Paper 6 in englischer Sprache vor (urn:nbn:de:hebis:30:3-478533).
Inhaltsverzeichnis:
Christian Reuter, Tanjev Schultz, Christian Stegbauer: Die Digitalisierung der Kommunikation: Gesellschaftliche Trends und der Wandel von Organisationen – Einleitung
Daniel Lambach: Digitale Welt und reale Welt – keine Gegensätze mehr
Leonard Reinecke: Schöne neue Smartphone-Welt? Psychologisches Wohlbefinden im Spannungsfeld von digitaler Autonomie und ständiger Vernetztheit
Christian Reuter: Fake News und manipulierte Meinungsbildung
Christian Stegbauer: Massenhafte Wutanfälle im Internet oder kann der Shitstorm jeden treffen?
Volker Schaeffer: „Wir haben schon immer in Bubbles gelebt“ – Chancen und Gefahren der Digitalisierung in den Medien
Angela Menig, Verena Zimmermann, Joachim Vogt: Die digitale Transformation der Arbeitswelt – Chance oder Risiko?
Stefan Aufenanger, Jasmin Bastian: Einsatz digitaler Technologie in Schulen
Angelika Böhling: Entwicklungszusammenarbeit goes digital– Chancen und Herausforderungen der digitalen Kommunikation von Nichtregierungsorganisationen
Josef Wiemeyer: Digitale Interaktion und Kommunikation im Sport
Die Publikation bietet einen Überblick zu den unterschiedlichen Formen und Herausforderungen des Wissenstransfers zwischen Universitäten, Ministerien, Behörden und Medien.
Inhaltsverzeichnis:
Birgitta Wolff, Georg Krausch und Hans Jürgen Prömel: Dialogorientierte Wissenschaftskommunikation als Gewinn für Universitäten und Praxis – Vorwort
Andreas Monz: Bedarf und Anforderungen an wissenschaftliche Expertise—der Blick aus der Praxis
Nina Janich: Warum Wissenschaftskommunikation manchmal so schwer ist … und auch deren Bewertung
Florian Meesmann: Dialog Wissenschaft und Medien—der Blick aus einer Rundfunkanstalt
Birgit Stark: Wissenschaftskommunikation in Zeiten rapiden Medienwandels
Manfred Niekisch: Dialoge der Vielfalt: Wissenschaft, Politik und Zivilgesellschaft
Heike Kaupp: Von der Wissenschaft in die Behördenpraxis
Nicole Deitelhoff: Mehr Mut zur Relevanz
Macrophage S1PR1 signaling alters angiogenesis and lymphangiogenesis during skin inflammation
(2019)
The bioactive lipid sphingosine-1-phosphate (S1P), along with its receptors, modulates lymphocyte trafficking and immune responses to regulate skin inflammation. Macrophages are important in the pathogenesis of psoriasiform skin inflammation and express various S1P receptors. How they respond to S1P in skin inflammation remains unknown. We show that myeloid specific S1P receptor 1 (S1PR1) deletion enhances early inflammation in a mouse model of imiquimod-induced psoriasis, without altering the immune cell infiltrate. Mechanistically, myeloid S1PR1 deletion altered the formation of IL-1β, VEGF-A, and VEGF-C, and their receptors’ expression in psoriatic skin, which subsequently lead to reciprocal regulation of neoangiogenesis and neolymphangiogenesis. Experimental findings were corroborated in human clinical datasets and in knockout macrophages in vitro. Increased blood vessel but reduced lymph vessel density may explain the exacerbated inflammatory phenotype in conditional knockout mice. These findings assign a novel role to macrophage S1PR1 and provide a rationale for therapeutically targeting local S1P during skin inflammation.
The website Sci-Hub enables users to download PDF versions of scholarly articles, including many articles that are paywalled at their journal’s site. Sci-Hub has grown rapidly since its creation in 2011, but the extent of its coverage has been unclear. Here we report that, as of March 2017, Sci-Hub’s database contains 68.9% of the 81.6 million scholarly articles registered with Crossref and 85.1% of articles published in toll access journals. We find that coverage varies by discipline and publisher, and that Sci-Hub preferentially covers popular, paywalled content. For toll access articles, we find that Sci-Hub provides greater coverage than the University of Pennsylvania, a major research university in the United States. Green open access to toll access articles via licit services, on the other hand, remains quite limited. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection, suggesting the toll access business model may become unsustainable.
Background: The aim of this study was to assess the knowledge and attitudes towards pregnancy-related issues of Zika virus (ZIKV) infection among general practitioners (GPs), a frontline healthcare worker group, in Indonesia.
Methods: A cross-sectional, online survey assessing knowledge and attitudes towards ZIKV infection on multiple-item scales was sent to GPs in the Sumatra and Java islands of Indonesia. The associations between independent factors and either knowledge or attitude were assessed with logistic regressions. The correlation and association between knowledge and attitude were estimated.
Results: We included 457 (53.7%) out of 850 responses in the analysis. Among these, 304 (66.5%) and 111 (24.2%) respondents had a good knowledge and attitude, respectively. No demographic, workplace, professional development, or experiential characteristics related to ZIKV infection were associated with knowledge. In the multivariate analysis, only contact experience was associated with attitude. There was a significant, positive correlation between knowledge and attitude scores.
Conclusions: Although knowledge of pregnancy-related complications of ZIKV infection is relatively high among GPs in Indonesia, more than 75% of them had a poor attitude towards pregnancy-related issues of Zika. Strategies for enhancing the capacity of GPs to develop positive attitudes and respond to ZIKV infection are needed.
Parabens and sorbic acid are commonly used as food preservatives due to their antimicrobial effect. However, their use in foods for infants and young children is not permitted in the European Union. Previous studies found these compounds in some gel-filled baby teethers, whereby parabens, which are well-known as endocrine disruptors, were identified in the polymer-based chewing surface consisting of ethylene-vinyl acetate (EVA). To assess the exposure of infants and young children to these products, the application of parabens in teethers should be thoroughly investigated. Therefore, the present study aimed to apply a representative migration test procedure combined with an accurate analytical method to examine gel-filled baby teethers without elaborate sample preparation, high costs, and long processing times. Accordingly, solid-phase extraction (SPE), in combination with a stable isotope dilution assay (SIDA) and subsequent gas chromatography–mass spectrometry (GC–MS) for analysis of methyl-, ethyl-, and n-propylparaben (MeP, EtP, and n-PrP), was found to be well-suited, with recoveries ranging from 93 to 99%. The study compared the release of these parabens from intact teether surfaces into water and saliva simulant under real-life conditions, with total amounts of detected parabens found to be in the range of 101–162 µg 100 mL−1 and 57–148 µg 100 mL−1, respectively. Furthermore, as a worst-case scenario, the release into water was examined using a long-term migration study.
Despite the popularity of direct democracy in recent decades, research on the actual output effects of popular decision-making is rare. This is especially true with regard to equality, where there are at least three major research gaps: 1) a lack of cross-national analyses; 2) insufficient investigation of the differential effects of different direct democratic instruments on equality; and 3) a failure to distinguish between different aspects of equality, i.e., socioeconomic, legal and political equality. This article takes a first step to tackle these shortcomings by looking at all national referenda in European democracies between 1990 and 2015, differentiating between mandatory, bottom-up and top-down referenda. We find that a large majority of successful direct democratic bills—regardless of which instrument is employed—are not related to equality issues. Of the remaining ones, there are generally more successful pro-equality bills than contra-equality ones, but the differences are rather marginal. Mandatory referenda tend to produce pro-equality outputs, but no clear patterns emerge for bottom-up and top-down referenda. Our results offer interesting, preliminary insights to the current debate on direct democracy, pointing to the conclusion that popular decision-making via any type of direct democratic instrument is neither curse nor blessing with regard to equality. Instead, it is necessary to look at other factors such as context conditions or possible indirect effects in order to get a clearer picture of the impacts of direct democracy on equality.
Zielsetzung: Ziel dieser Arbeit war es, den Einfluss des neuen, rauschoptimierten virtuell monoenergetischen Rekonstruktionsalgorithmus (VMI+) von abdominellen Dual-Energy CT (DECT) Aufnahmen bei Patienten mit gastrointestinalem Stromatumor (GIST) hinsichtlich der objektiven und subjektiven Bildqualität zu evaluieren sowie die Vorteile dessen im Vergleich zu den bislang verwendeten Algorithmen aufzuzeigen.
Material und Methoden: 45 DECT Datensätze von 21 Patienten mit GIST (12 Männer und 9 Frauen, durchschnittliches Alter: 63.4 ± 9.2 Jahre) wurden sowohl mit einem linear gemischten Algorithmus (M_0.6), mit dem traditionellen virtuell monoenergetischen Algorithmus (VMI) als auch mit dem rauschoptimierten VMI+ Algorithmus in 10 keV Intervallen von 40 bis 100 keV rekonstruiert. Zur objektiven Berechnung des Signal-zu-Rausch Verhältnisses („signal-to-noise ratio“=SNR) sowie des Kontrast-zu-Rausch Verhältnisses („contrast-to-noiseratio“=CNR) wurde die Signalabschwächung der GIST-Läsionen und abdomineller Metastasen in den drei Rekonstruktionsvarianten in Hounsfield Units (HU) gemessen. Die Beurteilung der subjektiven allgemeinen Bildqualität, der Abgrenzbarkeit der Läsionen, der Bildschärfe sowie des Bildrauschens im jeweiligen Rekonstruktionsalgorithmus wurde von drei Radiologen unter Verwendung von Likert-Skalen durchgeführt.
Ergebnisse: Die objektive Bildqualität wies die höchsten Werte in den 40 keV VMI+ Serien auf (SNR: 11.0 ± 4.7; CNR: 9.0 ± 4.1) und war somit signifikant besser als die M_0.6 Serie (SNR: 7.5 ± 2.8; CNR: 5.5 ± 2.7) und alle VMI Serien (bei allen P < 0.001). Bezüglich der subjektiven Bildqualität und der Bildschärfe wurden die 60 keV VMI+ Rekonstruktionen bevorzugt (Median: 5; P ≤ 0.008). Die subjektive Einschätzung bezüglich der Abgrenzbarkeit der GIST Läsionen erzielte die besten Werte in den 40 keV und 50 keV VMI+ Rekonstruktionen (beide Mediane: 4). Das Bildrauschen wurde in den 90 keV und 100 keV VMI und VMI+ Rekonstruktionen als am geringsten beurteilt (alle Mediane: 5).
Schlussfolgerung: Niedrigenergetische VMI+ Rekonstruktionen erhöhen signifikant das Signal-zu-Rausch Verhältnis sowie das Kontrast-zu-Rausch Verhältnis verglichen mit den traditionellen VMI Rekonstruktionen und der linear gemischten M_0.6 Bildserie und verbessern sowohl die objektive als auch die subjektive Bildqualität abdomineller DECT Aufnahmen bei Patienten mit GIST signifikant.
Astrocytes are increasingly perceived as active partners in physiological brain function and behaviour. The structural correlations of the glia–synaptic interaction are the peripheral astrocyte processes (PAPs), where ezrin and radixin, the two astrocytic members of the ezrin-radixin-moesin (ERM) family of proteins are preferentially localised. While the molecular mechanisms of ERM (in)activation appear universal, at least in mammalian cells, and have been studied in great detail, the actual ezrin and radixin kinases, phosphatases and binding partners appear cell type specific and may be multiplexed within a cell. In astrocytes, ezrin is involved in process motility, which can be stimulated by the neurotransmitter glutamate, through activation of the glial metabotropic glutamate receptors (mGluRs) 3 or 5. However, it has remained open how this mGluR stimulus is transduced to ezrin activation. Knowing upstream signals of ezrin activation, ezrin kinase(s), and membrane-bound binding partners of ezrin in astrocytes might open new approaches to the glial role in brain function. Ezrin has also been implicated in invasive behaviour of astrocytomas, and glial activation. Here, we review data pertaining to potential molecular interaction partners of ezrin in astrocytes, with a focus on PKC and GRK2, and in gliomas and other diseases, to stimulate further research on their potential roles in glia-synaptic physiology and pathology.
Purpose: To determine whether machine learning assisted-texture analysis of multi-energy virtual monochromatic image (VMI) datasets from dual-energy CT (DECT) can be used to differentiate metastatic head and neck squamous cell carcinoma (HNSCC) lymph nodes from lymphoma, inflammatory, or normal lymph nodes.
Materials and methods: A retrospective evaluation of 412 cervical nodes from 5 different patient groups (50 patients in total) having undergone DECT of the neck between 2013 and 2015 was performed: (1) HNSCC with pathology proven metastatic adenopathy, (2) HNSCC with pathology proven benign nodes (controls for (1)), (3) lymphoma, (4) inflammatory, and (5) normal nodes (controls for (3) and (4)). Texture analysis was performed with TexRAD® software using two independent sets of contours to assess the impact of inter-rater variation. Two machine learning algorithms (Random Forests (RF) and Gradient Boosting Machine (GBM)) were used with independent training and testing sets and determination of accuracy, sensitivity, specificity, PPV, NPV, and AUC.
Results: In the independent testing (prediction) sets, the accuracy for distinguishing different groups of pathologic nodes or normal nodes ranged between 80 and 95%. The models generated using texture data extracted from the independent contour sets had substantial to almost perfect agreement. The accuracy, sensitivity, specificity, PPV, and NPV for correctly classifying a lymph node as malignant (i.e. metastatic HNSCC or lymphoma) versus benign were 92%, 91%, 93%, 95%, 87%, respectively.
Conclusion: Machine learning assisted-DECT texture analysis can help distinguish different nodal pathology and normal nodes with a high accuracy.
Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Resulting fibrosis and portal hypertension, as a possible secondary event, may necessitate treatment. Overexpression of mouse renin in the transgenic rat model, TGR(mREN2)27, leads to spontaneous development of NAFLD. Therefore, we used TGR(mREN2)27 rats as a model of NAFLD where we hypothesized increased susceptibility and investigated fibrosis and portal hypertension and associated pathways. 12-week old TGR(mREN2)27 rats received either cholestatic (BDL) or toxic injury (CCl4 inhalation). Portal and systemic hemodynamic assessments were performed using microsphere technique with and without injection of the Janus-Kinase 2 (JAK2) inhibitor AG490 or the non-peptidic Ang(1-7) agonist, AVE0991. The extent of liver fibrosis was assessed in TGR(mREN2)27 and wild-type rats using standard techniques. Protein and mRNA levels of profibrotic, renin-angiotensin system components were assessed in liver and primary hepatic stellate cells (HSC) and hepatocytes. TGR(mREN2)27 rats developed spontaneous, but mild fibrosis and portal hypertension due to the activation of the JAK2/Arhgef1/ROCK pathway. AG490 decreased migration of HSC and portal pressure in isolated liver perfusions and in vivo. Fibrosis or portal hypertension after cholestatic (BDL) or toxic injury (CCl4) was not aggravated in TGR(mREN2)27 rats, probably due to decreased mouse renin expression in hepatocytes. Interestingly, portal hypertension was even blunted in TGR(mREN2)27 rats (with or without additional injury) by AVE0991. TGR(mREN2)27 rats are a suitable model of spontaneous liver fibrosis and portal hypertension but not with increased susceptibility to liver damage. After additional injury, the animals can be used to evaluate novel therapeutic strategies targeting Mas.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Neuropathic pain is a debilitating and commonly treatment-refractory condition requiring novel therapeutic options. Accumulating preclinical studies indicate that the potassium channel Slack (KNa1.1) contributes to the processing of neuropathic pain, and that Slack activators, when injected into mice, ameliorate pain-related hypersensitivity. However, whether Slack activation might reduce neuropathic pain in humans remains elusive. Here, we evaluated the tolerability and analgesic efficacy of loxapine, a first-generation antipsychotic drug and Slack activator, in neuropathic pain patients. We aimed to treat 12 patients with chronic chemotherapy-induced, treatment-refractory neuropathic pain (pain severity ≥ 4 units on an 11-point numerical rating scale) in a monocentric, open label, proof-of-principle study. Patients received loxapine orally as add-on analgesic in a dose-escalating manner (four treatment episodes for 14 days, daily dose: 20, 30, 40, or 60 mg loxapine) depending on tolerability and analgesic efficacy. Patient-reported outcomes of pain intensity and/or relief were recorded daily. After enrolling four patients, this study was prematurely terminated due to adverse events typically occurring with first-generation antipsychotic drugs that were reported by all patients. In two patients receiving loxapine for at least two treatment episodes, a clinically relevant analgesic effect was found at a daily dose of 20–30 mg of loxapine. Another two patients tolerated loxapine only for a few days. Together, our data further support the hypothesis that Slack activation might be a novel strategy for neuropathic pain therapy. However, loxapine is no valid treatment option for painful polyneuropathy due to profound dopamine and histamine receptor-related side effects.
Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02820519.
Der DNA-Translokator von T. thermophilus HB27, ebenso wie Typ-IV-Pili (T4P), sind Multiproteinkomplexe, die die Membranen und das Periplasma durchspannen. Sie sind ähnlich aufgebaut und enthalten identische Proteine. Der DNA-Translokator vermittelt Transport von DNA in das Zellinnere während der natürlichen Transformation. T4P sind filamentöse Zellorganellen, die an der inneren Membran assembliert werden und bis zu mehrere Mikrometer aus der Zelle hinausragen. Sie dienen der Anhaftung und Fortbewegung der Zellen auf Oberflächen.
Das Ziel dieser Arbeit war es, die Funktionen einzelner Komponenten der Komplexe und ihrer Proteindomänen bei der natürlichen Transformation, der T4P-Assemblierung und den durch T4P vermittelten Funktionen Adhäsion und „twitching motility“ aufzuklären.
Es sind neun Proteine bekannt, die eine duale Rolle als Komponenten des DNA-Translokators und des T4P spielen. Eines dieser Proteine ist die Assemblierungs-ATPase PilF, die Hexamere bildet. Diese cytoplasmatischen ATPase-Komplexe stellen die Energie für die Assemblierung der T4P bereit, ebenso wie für die Aufnahme freier DNA. Es ist jedoch bisher nicht geklärt, wie die durch PilF bereitgestellte Energie auf die anderen Komponenten des DNA-Translokators/T4P übertragen wird.
In dieser Arbeit konnte gezeigt werden, dass PilF an das cytoplasmatische Protein PilM des T4P und DNA-Translokators bindet. Zudem konnten Proteinkomplexe bestehend aus den Proteinen PilM, PilN und PilO heterolog produziert und aus Zellmembranen koisoliert werden. PilF interagierte mit diesen PilMNO-Komplexen via PilM. Diese Interaktionen führt zur Stimulierung der ATPase-Aktivität von PilF. Dies deutet an, dass PilM ein Kupplungsprotein ist, welches die Assemblierungs-ATPase PilF physisch und funktionell mit dem T4P/DNA-Translokator über den PilMNO-Komplex verbindet.
Neben PilF standen Präpiline von T. thermophilus im Fokus dieser Arbeit. Präpiline sind Vorläuferproteine, die zu Pilinen prozessiert werden und als solche dann die Untereinheiten der Pilus-Strukturen bilden.
Zusammenfassend konnten die Rollen einzelner Präpilin-ähnlicher Proteine bei T4P-assoziierten Funktionen geklärt werden und es konnten erste Analysen zur Charakterisierung des weitestgehend unbekannten Proteins ComZ durchgeführt werden. Desweiteren liefert diese Arbeit Hinweise darauf, dass die membranassoziierten Proteine PilM, PilN und PilO Kupplungsproteine sind, die PilF mit den periplasmatischen Komponenten des T4P/DNA-Translokators verbinden und dadurch die ATPase-Aktivität von PilF stimulieren. Die Rollen einzelner Proteindomänen von PilF und PilM bei der Protein-Protein-Interaktion und der Bindung von Liganden wurden aufgeklärt, sowie ihre Funktionen bei den T4P-vermittelten Funktionen und der natürlichen Transformation.
Seit dem 28. Juni 2019 ist in der hessischen Landeshauptstadt eine der größten privaten Jugendstil-Sammlungen Europas in einer Dauerausstellung zu sehen. Mit seiner großzügigen Schenkung hat der Kunstsammler Ferdinand Wolfgang Neess bereits vor zwei Jahren 570 Werke seiner in einem halben Jahrhundert zusammengetragenen Sammlung von Inkunabeln des internationalen Jugendstils dem Landesmuseum Wiesbaden vermacht. Seitdem wurde an der Präsentation dieser einmaligen Objekte im Südflügel des Museums gearbeitet, die nun seit knapp zwei Monaten der Öffentlichkeit zugänglich sind. ...
Background: Complications after surgery for esophageal cancer are associated with significant resource utilization. The aim of this study was to analyze the economic burden of two frequently used endoscopic treatments for anastomotic leak management after esophageal surgery: Treatment with a Self-expanding Metal Stent (SEMS) and Endoscopic Vacuum Therapy (EVT).
Materials and methods: Between January 2012 and December 2016, we identified 60 German-Diagnosis Related Group (G-DRG) cases of patients who received a SEMS and / or EVT for esophageal anastomotic leaks. Direct costs per case were analyzed according to the Institute for Remuneration System in Hospitals (InEK) cost-accounting approach by comparing DRG payments on the case level, including all extra fees per DRG catalogue.
Results: In total, 60 DRG cases were identified. Of these, 15 patients were excluded because they received a combination of SEMS and EVT. Another 6 cases could not be included due to incomplete DRG data. Finally, N = 39 DRG cases were analyzed from a profit-center perspective. A further analysis of the most frequent DRG code -G03- including InEK cost accounting, revealed almost twice the deficit for the EVT group (N = 13 cases, € - 9.282 per average case) compared to that for the SEMS group (N = 9 cases, € - 5.156 per average case).
Conclusion: Endoscopic treatments with SEMS and EVT for anastomotic leaks following oncological Ivor Lewis esophagectomies are not cost-efficient for German hospitals. Due to longer hospitalization and insufficient reimbursements, EVT is twice as costly as SEMS treatment. An adequate DRG cost compensation is needed for SEMS and EVT.
This article presents an analysis of the police television series A Touch of Frost (Yorkshire Television, 1992) and the crime novels by Rodney Wingfield upon which it is based.
In order to analyse the way the protagonist, Inspector Jack Frost, is characterised in either version, data is drawn from the pilot episode of the series and Wingfield’s debut novel Frost at Christmas (1984). Wingfield was less than impressed with television’s version of Frost, stating, ‘He just isn’t my Frost’. The rationale for this article is to apply established models in stylistics to investigate the differences between the original and the adaptation. A core motivation for stylistics is to ‘support initial impressions in various extracts’ readings’ and to ‘describe the readers’ response with some precision’ (Gregoriou 2007: 19); this article therefore offers a close linguistic explanation for an author’s dissatisfaction with the adaptation of his own work. The famously reticent Wingfield did not elaborate in detail on why he disapproved of the television version of Frost, although several critics observed that Wingfield felt television had ‘softened’ his creation. This article contends that ‘softness’ is represented in language through politeness strategies adopted by speakers whilst impoliteness represents the ‘tougher’ speech of Wingfield’s original iteration of Jack Frost. In order to demonstrate this contention, this study will analyse pragmatic elements of the dialogue of both novel and television versions of Frost through the analytical framework for impoliteness developed by Culpeper (1996; 2010). This framework will be integrated into the model for analysing the elements of narrative outlined by Simpson and Montgomery (1995), in turn suggesting an elaboration of this model. In investigating whether television’s Jack Frost is ‘softer’ than the character envisaged by Wingfield, free direct speech and accompanying physical behaviour in novel and television adaptation are analysed, focussing on whether the perceived softness of the latter has been partly achieved by making the speech of Frost less impolite on television.
Interleukin (IL)-18 and IL-22 are key components of cytokine networks that play a decisive role in (pathological) inflammation, host defense, and tissue regeneration. Tight regulation of cytokine-driven signaling, inflammation, and immunoactivation is supposed to enable nullification of a given deleterious trigger without mediating overwhelming collateral tissue damage or even activating a cancerous face of regeneration. In fact, feedback regulation by specific cytokine opponents is regarded as a major means by which the immune system is kept in balance. Herein, we shine a light on the interplay between IL-18 and IL-22 and their opponents IL-18 binding protein (IL-18BP) and IL-22BP in order to provide integrated information on their biology, pathophysiological significance, and prospect as targets and/or instruments of therapeutic intervention.
Forschen und Kuratieren sind Kerntätigkeitsbereiche von KunsthistorikerInnen. Genau das tun gerade junge NachwuchswissenschaftlerInnen am Kunstgeschichtlichen Institut der Goethe-Universität. In dem auf zwei Jahre angelegten Forschungs- und Ausstellungsprojekt "Die Porträtsammlung der Frankfurter Patrizierfamilie Holzhausen aus kunst- und kulturhistorischer Sicht" haben Masterstudierende der Kunstgeschichte und des Masterstudiengangs Curatorial Studies die Gelegenheit, am Puls der Forschung mitzuarbeiten. Unter der Leitung von Prof. Dr. Jochen Sander erlernen sie in einer Serie von drei Hauptseminaren, worauf es in der wissenschaftlichen Praxis und beim Ausstellungsmachen ankommt. ...
Endometriosis represents nowadays a real burden for the patients as well as for the physicians, as it requires surgical and/or medical treatment, often long – termed and repeated. Moreover, the high costs necessary to diagnose and treat endometriosis represent a real economic burden, being comparable to other chronic diseases like diabetes or rheumatoid arthritis. Therefore, the physicians dealing with this disease should take into account not only the efficacy of the treatment, but also the economic aspects and patients compliance.
The present paper analyses the efficiency of progestins (lynestrenol and medrogestone) in endometriosis as a cost – effective, but forgotten medical therapy of the disease. Our study underlines the good tolerability of progestins, as they have limited side effects, the compliance of patients being high. They are also low-cost medications, which could represent an effective alternative method in the endometriosis treatment, especially in less – developed countries that cannot afford the higher therapeutic costs.
Die Keksfabrik, das alte Backsteingemäuer, dessen Schornstein hinter der Universitätsbibliothek in die Höhe ragt, beherbergt seit vielen Jahrzehnten das Institut für Kunstpädagogik. Auf besondere Weise hat dieser Ort Arbeit und Lehre beeinflusst; nicht zuletzt durch die Aneignung der Räumlichkeiten als Werkstätten und Ateliers. Doch der Umzug auf den Campus Westend rückt näher und noch bevor die Erinnerung an das markante Gebäude verblasst, soll die Geschichte dieses besonderen Standortes, sowie sein Einfluss auf das Institutsleben in einer Ausstellung beleuchtet werden. Eröffnet wird sie an diesem Donnerstag ab 18 Uhr mit einem Rundgang. ...
Background: Patient Reported Outcomes (PRO) are gaining more and more importance in the context of clinical trials. The assessment of PRO is frequently performed by questionnaires where the multiple items of a questionnaire are usually pooled within summarizing scores. These scores are used as variables to measure subjective aspects of treatments and diseases. In clinical research, the calculation of these scores is mostly kept very simple, e.g. by a simple summation of item values. In the medical literature, there is hardly any guidance for performing a refinements of questionnaires and for deducing adequate scores. In contrast, in psychometric literature, there are plenty of more sophisticated methods, which overcome typical assumptions made in traditional (sum) scores, however to the prize of more complicated algorithms, which might be difficult to communicate. When faced with the practical task to refine an existing questionnaire, there exist a clear gap of guidance for applied medical researchers. By this article we try to fill this important gap between psychometric theory and medical application by illustrating our methodological choices on the example of a clinical PRO questionnaire.
Methods: Based on our experiences with the refinement of the BCTOS, a PRO questionnaire to assess aesthetic and function after breast conserving therapy in breast cancer patients, we present the following general steps that we performed by refining the BCTOS questionnaire and its scores: 1. Refinement of the length of the questionnaire and the (item-factor) structure. 2. Selection of the factor score estimation method. 3. Validation of the refined questionnaire and scores with respect to validity, reliability and structure based on a validation cohort.
Results: Our step-step-step procedure helped us to shorten the current form of the BCTOS and to redefine the factor structure. By this, the compliance of patients can be increased and the interpretation of the results becomes more coherent.
Conclusions: We present a step-by-step procedure to refine an existing medical questionnaire along with its scores illustrated and discussed by the refinement of the BCTOS.
Trial registration: Due to the character of the study (no intervention study), no registration was performed.
Early, non-invasive sensing of sustained hyperglycemia in mice using millimeter-wave spectroscopy
(2019)
Diabetes is a very complex condition affecting millions of people around the world. Its occurrence, always accompanied by sustained hyperglycemia, leads to many medical complications that can be greatly mitigated when the disease is treated in its earliest stage. In this paper, a novel sensing approach for the early non-invasive detection and monitoring of sustained hyperglycemia is presented. The sensing principle is based on millimeter-wave transmission spectroscopy through the skin and subsequent statistical analysis of the amplitude data. A classifier based on functional principal components for sustained hyperglycemia prediction was validated on a sample of twelve mice, correctly classifying the condition in diabetic mice. Using the same classifier, sixteen mice with drug-induced diabetes were studied for two weeks. The proposed sensing approach was capable of assessing the glycemic states at different stages of induced diabetes, providing a clear transition from normoglycemia to hyperglycemia typically associated with diabetes. This is believed to be the first presentation of such evolution studies using non-invasive sensing. The results obtained indicate that gradual glycemic changes associated with diabetes can be accurately detected by non-invasively sensing the metabolism using a millimeter-wave spectral sensor, with an observed temporal resolution of around four days. This unprecedented detection speed and its non-invasive character could open new opportunities for the continuous control and monitoring of diabetics and the evaluation of response to treatments (including new therapies), enabling a much more appropriate control of the condition.
An increased expression and cytoplasmic abundance of the ubiquitous RNA binding protein human antigen R (HuR) is critically implicated in the dysregulated control of post-transcriptional gene expression during colorectal cancer development and is frequently associated with a high grade of malignancy and therapy resistance. Regardless of the fact that HuR elicits a broad cell survival program by increasing the stability of mRNAs coding for prominent anti-apoptotic factors, recent data suggest that HuR is critically involved in the regulation of translation, particularly, in the internal ribosome entry site (IRES) controlled translation of cell death regulatory proteins. Accordingly, data from human colon carcinoma cells revealed that HuR maintains constitutively reduced protein and activity levels of caspase-2 through negative interference with IRES-mediated translation. This review covers recent advances in the understanding of mechanisms underlying HuR’s modulatory activity on IRES-triggered translation. With respect to the unique regulatory features of caspase-2 and its multiple roles (e.g., in DNA-damage-induced apoptosis, cell cycle regulation and maintenance of genomic stability), the pathophysiological consequences of negative caspase-2 regulation by HuR and its impact on therapy resistance of colorectal cancers will be discussed in detail. The negative HuR-caspase-2 axis may offer a novel target for tumor sensitizing therapies.