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We combine ultrafast X-ray diffraction (UXRD) and time-resolved Magneto-Optical Kerr Effect (MOKE) measurements to monitor the strain pulses in laser-excited TbFe2/Nb heterostructures. Spatial separation of the Nb detection layer from the laser excitation region allows for a background-free characterization of the laser-generated strain pulses. We clearly observe symmetric bipolar strain pulses if the excited TbFe2 surface terminates the sample and a decomposition of the strain wavepacket into an asymmetric bipolar and a unipolar pulse, if a SiO2 glass capping layer covers the excited TbFe2 layer. The inverse magnetostriction of the temporally separated unipolar strain pulses in this sample leads to a MOKE signal that linearly depends on the strain pulse amplitude measured through UXRD. Linear chain model simulations accurately predict the timing and shape of UXRD and MOKE signals that are caused by the strain reflections from multiple interfaces in the heterostructure.
Die funktionelle Charakterisierung von therapeutisch relevanten Proteinen kann bereits durch die Bereitstellung des Zielproteins in adäquaten Mengen limitierend sein. Dies trifft besonders auf Membranproteine zu, die aufgrund von zytotoxischen Effekten auf die Produktionszelllinie und der Tendenz Aggregate zu bilden, in niedrigen Ausbeuten an aktivem Protein resultieren können. Der lebende Organismus kann durch die Verwendung von translationsaktiven Zelllysaten umgangen werden- die Grundlage der zellfreien Proteinsynthese. Zu Beginn der Arbeit wurde die ATP-abhängige Translation eines Lysates auf der Basis von kultivierten Insektenzellen (Sf21) analysiert. Für diesen Zweck wurde ein ATP-bindendes Aptamer eingesetzt, durch welches die Translation der Nanoluziferase reguliert werden konnte. Durch die dargestellte Applizierung von Aptameren, könnten diese zukünftig in zellfreien Systemen für die Visualisierung der Transkription und Translation eingesetzt werden, wodurch zum Beispiel komplexe Prozesse validiert werden können.
Neben der reinen Proteinherstellung können Faktoren wie posttranslationale Modifikationen sowie eine Integration in eine lipidische Membran essentiell für die Funktionalität des Membranproteins sein. Im zweiten Abschnitt konnte, im zellfreien Sf21-System, für den G-Protein-gekoppelten Rezeptor Endothelin B sowohl eine Integration in die endogen vorhandenen Endoplasmatisch Retikulum-basierten Membranstrukturen als auch Glykosylierungen, identifiziert werden.
Auf der Grundlage der erfolgreichen Synthese des ET-B-Rezeptors wurden verschiedene Methoden zur Fluoreszenzmarkierung des Adenosin-Rezeptors A2a (Adora2a) angewandt und optimiert. Im dritten Abschnitt wurde der Adora2a mit Hilfe einer vorbeladenen tRNA, welche an eine fluoreszierende Aminosäure gekoppelt war, im zellfreien Chinesischen Zwerghamster Ovarien (CHO)-System markiert. Zusätzlich konnte durch den Einsatz eines modifizierten tRNA/Aminoacyl-tRNA-Synthetase-Paares eine nicht-kanonische Aminosäure an Position eines integrierten Amber-Stopcodon in die Polypeptidkette eingebaut und die funktionelle Gruppe im Anschluss an einen Fluoreszenzfarbstoff gekoppelt werden. Aufgrund des offenen Charakters eignen sich zellfreie Proteinsynthesesysteme besonders für eine Integration von exogenen Komponenten in den Translationsprozess. Mit Hilfe der Fluoreszenzmarkierung wurde eine ligandvermittelte Konformationsänderung im Adora2a über einen Biolumineszenz-Resonanzenergietransfer detektiert. Durch die Etablierung der Amber-Suppression wurde darüber hinaus das Hormon Erythropoetin pegyliert, wodurch Eigenschaften wie Stabilität und Halbwertszeit des Proteins verändert wurden.
Zu guter Letzt wurde ein neues tRNA/Aminoacyl-tRNA-Synthetase-Paar auf Basis der Methanosarcina mazei Pyrrolysin-Synthetase etabliert, um das Repertoire an nicht-kanonischen Aminosäuren und den damit verbundenen Kopplungsreaktionen zu erweitern. Zusammenfassend wurden die Potenziale zellfreier Systeme in Bezug auf der Herstellung von komplexen Membranproteinen und der Charakterisierung dieser durch die Einbringung einer positionsspezifischen Fluoreszenzmarkierung verdeutlicht, wodurch neue Möglichkeiten für die Analyse und Funktionalisierung von komplexen Proteinen geschaffen wurden.
Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin‐induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6‐mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration‐related way. This effect was confirmed in whole‐cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin‐1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine‐tuning their physical properties.
Domain-specific physical activity patterns and cardiorespiratory fitness among adults in Germany
(2019)
Background Studies show that occupational physical activity (OPA) has less health-enhancing effects than leisure-time physical activity (LTPA). The spare data available suggests that OPA rarely includes aerobic PAs with little or no enhancing effects on cardiorespiratory fitness (CRF) as a possible explanation. This study aims to investigate the associations between patterns of OPA and LTPA and CRF among adults in Germany. Methods 1,204 men and 1,303 women (18-64 years), who participated in the German Health Interview and Examination Survey 2008-2011, completed a standardized sub-maximal cycle ergometer test to estimate maximal oxygen consumption (VO2max). Job positions were coded according to the level of physical effort to construct an occupational PA index and categorized as low vs. high OPA. LTPA was assessed via questionnaires and dichotomized in no vs. any LTPA participation. A combined LTPA/OPA variable was used (high OPA/ LTPA, low OPA/LTPA, high OPA/no LTPA, low OPA/no LTPA). Information on potential confounders was obtained via questionnaires (e.g., smoking and education) or physical measurements (e.g., waist circumference). Multi-variable logistic regression was used to analyze associations between OPA/LTPA patterns and VO2max. Results Preliminary analyses showed that less-active men were more likely to have a low VO2max with odds ratios (ORs) of 0.80 for low OPA/LTPA, 1.84 for high OPA/no LTPA and 3.46 for low OPA/no LTPA compared to high OPA/LTPA. The corresponding ORs for women were 1.11 for low OPA/LTPA, 3.99 for high OPA/no LTPA and 2.44 for low OPA/no LTPA, indicating the highest likelihood of low fitness for women working in physically demanding jobs and not engaging in LTPA. Conclusions Findings confirm a strong association between LTPA and CRF and suggest an interaction between OPA and LTPA patterns on CRF within the workforce in Germany. Women without LTPA are at high risk of having a low CRF, especially if they work in physically demanding jobs. Key messages Women not practicing leisure-time physical activity are at risk of having a low cardiorespiratory fitness, especially if they work in physically demanding jobs. Different impact of domains of physical activity should be considered when planning interventions to enhance fitness among the adult population.
New ionogels (IGs) were prepared by combination of a series of sulfonate-based ionic liquids (ILs), 1-methyl-3-(4-sulfobutyl)imidazolium para-toluenesulfonate [BmimSO(3)][pTS], 1-methyl-1-butylpiperidiniumsulfonate para-toluenesul-fonate [BmpipSO(3)] [pTS], and 1-methyl-3-(4-sulfobutyl) imidazolium methylsulfonate [BmimSO(3)H][MeSO3] with a commercial stereolithography photoreactive resin. The article describes both the fundamental properties of the ILs and the resulting IGs. The IGs obtained from the ILs and the resin show high ionic conductivity of up to ca. 0.7.10(-4) S/cm at room temperature and 3.4-10(-3) S/cm at 90 degrees C. Moreover, the IGs are thermally stable to about 200 degrees C and mechanically robust. Finally, and most importantly, the article demonstrates that the IGs can be molded three-dimensionally using stereolithography. This provides, for the first time, access to IGs with complex 3D shapes with potential application in battery or fuel cell technology.
Effects of Aerobic and Resistance Exercise on Cardiovascular Parameters for People Living With HIV
(2019)
People living with HIV (PLWH) have limited exercise capacity because of anemia, neuromuscular disorders, and pulmonary limitations. We used a meta-analysis to examine the effect of aerobic and resistance exercise alone and in combination on cardiovascular parameters. Subgroup meta-analyses were conducted and long-term effects of exercise were investigated. A systematic literature search was conducted up to July/August 2017. The Physiotherapy Evidence Database-scale was used to rate quality and assess the risk of bias on the papers. Standardized mean differences (SMDs) were calculated to assess the effect of exercise. Posttreatment comparison between the exercise and control groups revealed moderate and large effect sizes in favor of the intervention group for VO2max (SMD50.66, p < .0001) and the 6-minute walk test (SMD = 1.11, p = .0001). Exercise had a positive effect on cardiovascular parameters in PLWH. Exercise can be a prevention factor for PLWH dealing with multiple comorbidities.
Transverse dispersion, or tracer spreading orthogonal to the mean flow direction, which is relevant e.g, for quantifying bio-degradation of contaminant plumes or mixing of reactive solutes, has been studied in the literature less than the longitudinal one. Inferring transverse dispersion coefficients from field experiments is a difficult and error-prone task, requiring a spatial resolution of solute plumes which is not easily achievable in applications. In absence of field data, it is a questionable common practice to set transverse dispersivities as a fraction of the longitudinal one, with the ratio 1/10 being the most prevalent. We collected estimates of field-scale transverse dispersivities from existing publications and explored possible scale relationships as guidance criteria for applications. Our investigation showed that a large number of estimates available in the literature are of low reliability and should be discarded from further analysis. The remaining reliable estimates are formation-specific, span three orders of magnitude and do not show any clear scale-dependence on the plume traveled distance. The ratios with the longitudinal dispersivity are also site specific and vary widely. The reliability of transverse dispersivities depends significantly on the type of field experiment and method of data analysis. In applications where transverse dispersion plays a significant role, inference of transverse dispersivities should be part of site characterization with the transverse dispersivity estimated as an independent parameter rather than related heuristically to longitudinal dispersivity.
-Jill Rabea Zaun: Eduard Hildebrandts „Wunderbild“
in einem Brief von Alexander von Humboldt an Henriette Mendelssohn, geb. Meyer
-Ottmar Ette: Paris/Berlin/Havanna: Alexander von Humboldts transareale Wissenschaft und die Revolution nach der Revolution
-Frank Holl: Alexander von Humboldt und der Klimawandel
Mythen und Fakten
-Cettina Rapisarda: Antike Marmorarten nach Zoёga’s Bestimmungen. Alexander von Humboldts Sammlung und Gesteinsstudien in Rom
-Sandra Rebok: De la pintura de viaje a la fotografía: Alexander von Humboldt y la representación artística del Nuevo Mundo
-Ingo Schwarz: Der zweite Entdecker Kubas
Die 2011 von Sebastian Panwitz und Ingo Schwarz herausgegebene Korrespondenz Alexander von Humboldts mit den Mendelssohns dokumentiert ihre lebenslange Verbundenheit. Ein Brief von Humboldt an Henriette Mendelssohn, den die Mendelssohn-Gesellschaft von einem privaten Sammler erwarb, und der erst seit diesem Jahr in der Mendelssohn-Remise in Berlin-Mitte, in der Dauerausstellung Die Mendelssohns in der Jägerstraße zu sehen ist, war zum Zeitpunkt der Veröffentlichung noch nicht zugänglich. Dieser Brief lässt das gesellschaftliche und künstlerische Leben der Stadt um 1850 sichtbar werden und enthält einige Rätsel: Was hat es mit dem unkommentierten Zettel auf sich, auf dem ein nicht korrekt wiedergegebener Buchtitel der amerikanischen Autorin Harriet Beecher Stowe geschrieben steht und welches „Wunderbild“ erwähnt der weltberühmte Forschungsreisende in dem Brief an Henriette Mendelssohn?
Zero-shot learning in Language & Vision is the task of correctly labelling (or naming) objects of novel categories. Another strand of work in L&V aims at pragmatically informative rather than "correct" object descriptions, e.g. in reference games. We combine these lines of research and model zero-shot reference games, where a speaker needs to successfully refer to a novel object in an image. Inspired by models of "rational speech acts", we extend a neural generator to become a pragmatic speaker reasoning about uncertain object categories. As a result of this reasoning, the generator produces fewer nouns and names of distractor categories as compared to a literal speaker. We show that this conversational strategy for dealing with novel objects often improves communicative success, in terms of resolution accuracy of an automatic listener.