Trace-element modelling of melting in spinel peridotites

This study addresses three independent topics related to trace element modeling of spinel peridotites that are suggested by the pioneering work of Johnson et al. (1990) on abyssal harzburgites. First, the fractional non-modal melting equation derived by Johnson and coworkers (1990) is algebraically modified to present a one-element/two-phase model. This model suggests a simple test for estimating mantle heterogeneity in the source rock of spinel lherzolites. This model is applied to data from the literature for samples from Dreiser Weiher, Germany; San Luis Potosi, Mexico; and Western Victoria, Australia. Second, trace elements in clinopyroxenes of abyssal peridotites and continental spinel Iherzolite nodules from multiple localities are compared. Plots of Ti versus Zr, Na2O and REEs show data overlap in their distribution trends, and they are thought to have originated from broadly similar ratios in the source rock prior to partial melting and by generally similar melting processes. Third, a modal melting (MM) diagram for abyssal peridotites based on the Johnson et al. (1990) melting equation is constructed that illustrates how modal proportions of mineral phases in a spinel-lherzolitic mineral assemblage change as a function of F (degree of melting). In accordance with this model, a method is introduced that allows F to be calculated based solely on the modal composition for a particular sample. This model is calibrated with Ti data for Cpx in abyssal harzburgites, and the original mantle composition is calculated at F=0 and compared to other suggested primitive upper mantle compositions. The sensitivity of this diagram to variations in input parameters is also shown. A further calibration with experimentally-established reaction coefficients for the upper mantle melting reaction (Kinzler & Grove 1992a, b; Baker & Stolper 1993) is also carried out in order to test similarities between these two independent approaches. The calibration shows iterative values for the input parameter are in partial agreement with experimentally-derived reaction coefficients. While the resulting reaction coefficients confirm generation of olivine during melting as suggested by melting experiments, Opx and Cpx reaction coefficients show similar proportions (Cpx/Opx \u3c 1). This observation does not concur with experimentally-determined mantle melt reaction (Cpx/Opx ~ 2 for Kinzler & Grove (1992a) and Baker & Stolper (1993)). A satisfactory link between trace-element modelling and high P-T melting experiments could therefore not be obtained through the MM-model

Synthese prenylierter Chalkone aus Hopfen und Bestimmung ihrer cytotoxischen und antioxidativen Aktivität

Prenylierte Chalkone sind die dominierenden Verbindungen in der phenolischen Fraktion der Fruchtstände des Hopfens (Humulus lupulus L.). Der wichtigste Vertreter dieser Substanzklasse in H. lupulus ist das Xanthohumol. Das Ziel der vorliegenden Arbeit bestand in der Etablierung einer universellen, nachhaltigen und möglichst einfachen chemischen Synthese des Xanthohumols und möglichst vieler Sekundärstoffmetabolite aus der Chalkonfraktion des Hopfens. Dabei wurde es als wichtig angesehen möglichst wenige universale Synthesebausteine zu verwenden und auch solche Syntheseschritte zu wählen, die in ihrer Reihenfolge möglichst frei kombinierbar sind, um dadurch auf einfachem Weg eine große Strukturvielfalt zu erhalten. Zunächst wurde eine effiziente Synthese für das Xanthohumol entwickelt. Im weiteren Focus stand die Synthese von zahlreichen Minorkomponenten aus Hopfen, die bisher über die Isolierung kaum zugänglich waren sowie die Darstellung auch nicht natürlicher Derivate, um in nachfolgenden pharmakologischen Untersuchungen Beziehungen zwischen Struktur und Aktivität ermitteln zu können. Zu den synthetisierten Substanzen aus dem Sekundärstoffspektrum des Hopfens gehören u. a. Desmethylxanthohumol, Xanthogalenol, 4�-OMetyhlxanthohumol, 5�-Prenylxantho-humol, Xanthohumol C, 1��,2��-Dihydroxanthohumol und 3�-Geranylchalconaringenin. Daneben umfasst das Spektrum synthetisierter Verbindungen auch nicht prenylierte Chalkone wie das Flavokawin und das Helichrysetin sowie Substanzen, die als Phase-I-Metaboliten des Xanthohumols identifiziert worden sind wie das Xanthohumol H und das 3-Hydroxyxanthohumol. Nicht natürliche Abkömmlinge wurden durch Variation der Substitutionsmuster in A- und B-Ring erzeugt wobei die Einführung zusätzlicher Hydroxylgruppen und die Variation der Anzahl und Stellung der Methoxygruppen im Vordergrund standen. Die einzelnen Chalkone wurden dabei durch eine basenkatalysierte Aldol-Kupplung eines entsprechend substituierten und MOM-geschützten Acetophenons (A-Ring) mit einem MOM-geschützten Hydroxybenzaldehyd-Derivat (B-Ring) erhalten, der als finalem Schritt eine Abspaltung der MOM-Gruppen folgte. Es wurde damit begonnen die pharmakologische Aktivität aller hergestellten Substanzen zu untersuchen. Dazu wurden die Verbindungen an einer Gebärmutterhalskarzinomzelllinie (HeLa) auf ihre Zytotoxizität in einem MTT-Assay getestet. Darüber hinaus wurde die antioxidative Aktivität in einem ORAC-Fluorescein Assay bestimmt. Einige der Minorverbindungen wie das Xanthohumol H oder das Desmethylxanthohumol zeigten im ORAC Assay eine deutliche höhere Aktivität als das Xanthohumol. Unter den nicht natürlich vorkommenden Verbindungen war das 2�-Methyl-Analagon des Xanthohumols, das Xanthoflorianol, im ORAC-Test besonders aktiv. Gegenüber HeLa Zellen erwies sich der Phase-I-Metabolit 3�-Hydroxyxanthohumol als eine der aktivsten Verbindungen. Als Resümee lässt sich festhalten, dass die Etablierung eines universal anwendbaren, effizienten und nachhaltigen Syntheseweges für ein breites Strukturspektrum von Chalkonen gelungen ist. Die pharmakologischen Arbeiten zeigten, dass auch von den Minorverbindungen im Hopfen wie auch von den bisher untersuchten Phase-I-Metaboliten des Xanthohumols eine potente pharmakologische Aktivität erwartet werden kann, und eine breite pharmakologische Charakterisierung in Zukunft lohnenswert erscheint

Details acquired from medical history and patients’ experience of empathy – two sides of the same coin

BACKGROUND: History taking and empathetic communication are two important aspects in successful physician-patient interaction. Gathering important information from the patient’s medical history is needed for effective clinical decision making while empathy is relevant for patient satisfaction. We wanted to investigate whether medical students near graduation are able to combine both skills as required in daily medical practice. METHODS: Thirty near graduates from Hamburg Medical School participated in an assessment for clinical competences including a consultation hour with five standardized patients. Each patient interview was videotaped and standardized patients rated participants with the CARE questionnaire for consultation and relational empathy. All videotaped interviews were rated with a checklist based on the number of important medical aspects for each case. Data were analysed with the linear mixed model to correct for random effects. Regression analysis was performed to look for correlations between the number of questions asked by a participant and their respective empathy rating. RESULTS: Of the 123 aspects that could have been gathered in total, students only requested 56.4% (95% CI 53.5-59.3). While no difference between male and female participants was found, a significant difference (p < .001) was observed between the two parts of the checklist with 61.1% (95% CI 57.9-64.3) of aspects asked for in part 1 (patient’s symptoms) versus 52.0 (95 47.4-56.7) in part 2 (further history). All female standardized patients combined rated female participants (mean score 14.2, 95% CI 12.3-16.3) to be significantly (p < .01) more empathetic than male participants (mean score 19.2, 95% CI 16.3-22.6). Regression analysis revealed no correlation between the number of medical aspects gathered by a participant and his or her respective empathy score given by the standardized patient in the CARE questionnaire. CONCLUSION: Gathering sufficient medical data from a patient’s history and empathetic communication are two completely separate sides of the coin of history taking. While both skills have to be acquired during medical school training with particular focus on their respective learning objectives, medical students need to be provided with additional learning and feedback opportunities where they can be observed exercising both skills combined as required in physicians’ daily practice

Modularity and Architecture of PLC-based Software for Automated Production Systems: An analysis in industrial companies

Adaptive and flexible production systems require modular and reusable software especially considering their long term life cycle of up to 50 years. SWMAT4aPS, an approach to measure Software Maturity for automated Production Systems is introduced. The approach identifies weaknesses and strengths of various companie's solutions for modularity of software in the design of automated Production Systems (aPS). At first, a self assessed questionnaire is used to evaluate a large number of companies concerning their software maturity. Secondly, we analyze PLC code, architectural levels, workflows and abilities to configure code automatically out of engineering information in four selected companies. In this paper, the questionnaire results from 16 German world leading companies in machine and plant manufacturing and four case studies validating the results from the detailed analyses are introduced to prove the applicability of the approach and give a survey of the state of the art in industry

Resilient modulus of subgrade soil taken from a trial pavement section

By producing H2O2, the NADPH oxidase Nox4 is involved in differentiation of mesenchymal cells. Exercise alters the composition of slow and fast twitch fibres in skeletal. Here we hypothesized that Nox4 contributes to exercise-induced adaptation such as changes in muscle metabolism or muscle fibre specification and studied this in wildtype and Nox4-/- mice.Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill induced a switch from fast twitch to intermediate fibres. However the induced muscle fibre switch was similar between Nox4-/- and wildtype mice. The same held true for exercise-induced expression of PGC1α or AMPK activation. Both are increased in response to exercise, but with no difference was observed between wildtype and Nox4-/- mice.Thus, exercise-induced muscle fibre switch is Nox4-independent

Lessons Learned from an Outbreak in Germany, 2012-2013

Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012–2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002–2014. Results Among the 148 IMD-cases notified from 01.01.2012–30.09.2013 in 18–59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5–1,10–8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5–1,10–8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002–2014 was lacking, clusters were more frequent in men aged 20–49 years. Molecular analysis of C:P1.5–1,10–8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control

Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS):A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases

The opportunistic pathogen Pseudomonas aeruginosa employs quorum sensing to govern the production of many virulence factors. Interference with quorum sensing signaling has therefore been put forward as an attractive approach to disarm this pathogen. Here, we analyzed the quorum quenching properties of natural and engineered (2-alkyl-)3-hydroxy-4(1H)-quinolone 2,4-dioxygenases (HQDs) that inactivate the P. aeruginosa signal molecule PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4(1H)-quinolone). When added exogenously to P. aeruginosa cultures, all HQDs tested significantly reduced the levels of PQS and other alkylquinolone-type secondary metabolites deriving from the biosynthetic pathway, such as the respiratory inhibitor 2-heptyl-4-hydroxyquinoline N-oxide. HQDs from Nocardia farcinica and Streptomyces bingchenggensis, which combine low K(M) values for PQS with thermal stability and resilience in the presence of P. aeruginosa exoproducts, respectively, attenuated production of the virulence factors pyocyanin and pyoverdine. A delay in mortality was observed when Galleria mellonella larvae were infected with P. aeruginosa suspensions treated with the S. bingchenggensis HQD or with inhibitors of alkylquinolone biosynthesis. Our data indicate that quenching of PQS signaling has potential as an anti-virulence strategy; however, an efficient anti-virulence therapy against P. aeruginosa likely requires a combination of agents addressing multiple targets

Die Internationalität der Rassenforschung im 20. Jahrhundert

Kühl S. Die Internationalität der Rassenforschung im 20. Jahrhundert. In: Foroutan N, Geulen C, Illmer S, Vogel K, Wernsing S, eds. Das Phantom "Rasse". Zur Geschichte und Wirkungsmacht von Rassismus. Schriften des Deutschen Hygiene-Museums Dresden. Vol 13. Köln: Böhlau; 2018: 105-111

Prof. Dr. med. Bernhard Riedel (1846-1916) und seine Leistungen auf dem Gebiet der Abdominalchirurgie: eine Analyse seiner Jenaer Operationstagebücher im Zeitraum von 1888 bis 1910

Mit der Entdeckung der Narkose im Jahre 1846 begann in der Medizin eine neue Ära, der ein enormer Aufschwung, insbesondere in der Chirurgie, in der zweiten Hälfte des 19. Jahrhunderts folgte. Im gleichen Jahr dieses Wendepunktes wurde auch Bernhard Carl Ludwig Moritz Riedel am 18. September in Laage in Mecklenburg geboren. In der vorliegenden Dissertation steht als Beitrag zur Geschichte der Medizinischen Fakultät Jenas Bernhard Riedels Leben und Wirken im Mittelpunkt. Dabei wird insbesondere die Zeit seines Chirurgischen Ordinariats an der Universität Jena von 1888 bis 1910 einschließlich seiner Lehrtätigkeit und Schüler wie Heinrich Haeckel (geb. 1859) oder Wilhelm Röpke (1873-1945) thematisiert. Als Zeugnisse seines Schaffens in Jena sind zwölf Bände seiner Operationstagebücher erhalten geblieben, die der Friedrich-Schiller-Universität Jena durch Riedels Nachkommen im April 1998 zur wissenschaftlichen Auswertung übergeben wurden. Die Analyse dieser Tagebücher bildet neben der Biografie Riedels einen weiteren Schwerpunkt der Arbeit. Abschließend wurden daraus Fallbeispiele ausgewählt, zu denen Bezüge aus Riedels wissenschaftlichen Schriften hergestellt werden. Bei der Auseinandersetzung mit dem Leben und Schaffen von Bernhard Riedel lernt man ihn als vielseitigen und ehrgeizigen Chirurgen kennen, durch dessen Ordinariat die Alma mater Jenensis über die thüringischen Grenzen hinaus Anerkennung erlangen konnte

Everolimus in Combination with Cyclosporin A as Pre- and Posttransplantation Immunosuppressive Therapy in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Everolimus (RAD001) is an mTOR inhibitor that has been successfully used as an immunosuppressant in solid-organ transplantation. Data in allogeneic hematopoietic stem cell transplantation (HSCT) is limited. This study aimed to investigate pharmacokinetics, safety, and efficacy of RAD001 in a canine allogeneic HSCT model. First, pharmacokinetics of RAD001 were performed in healthy dogs in order to determine the appropriate dosing. Doses of 0.25 mg RAD001 twice daily in combination with 15 mg/kg cyclosporin A (CsA) twice daily were identified as appropriate starting doses to achieve the targeted range of RAD001 (3-8 μg/L) when orally administered. Subsequently, 10 dogs were transplanted using 2 Gy total body irradiation (TBI) for conditioning and 0.25 mg RAD001 twice daily plus 15 mg/kg CsA twice daily for pre- and posttransplantation immunosuppression. Seven of the 10 transplanted dogs were maintained at the starting RAD001 dose throughout the study. For the remaining 3 dogs, dose adjustments were necessary. RAD001 accumulation over time did not occur. All dogs initially engrafted. Five dogs eventually rejected the graft (weeks 10, 10, 13, 27, and 56). Two dogs died of pneumonia (weeks 8 and 72) but were chimeric until then. Total cholesterol rose from median 4.1 mmol/L (3.5-5.7 mmol/L) before HSCT to 6.0 mmol/l (5.0-8.5 mmol/l) at day 21 after HSCT, but remained always within normal range. Changes in creatinine and triglyceride values were not observed. Long-term engraftment rates were inferior to sirolimus/CsA and mycophenolate mofetil (MMF)/CsA regimen, respectively. RAD001/CsA caused a more pronounced reduction of platelet counts to median 2 × 109/L (range: 0-21 × 109/L) and longer time to platelet recovery of 21 days (range: 14-24 days) compared with MMF/CsA. CsA c2h levels were significantly enhanced in the RAD001/CsA regimen, but c0h and area under the curve from 0 to 12 hours (AUC0-12h) values did not differ compared with an MMF/CsA immunosuppression. In summary, immunosuppression consisting of RAD001 and CsA is well tolerated but not as efficient as with other established immunosuppressants in a canine nonmyeloablative HSCT regimen. Hence, our study does not support the application of RAD001/CsA as standard practice in this setting