Immobilisierbare Pyrenderivate zur Anwendung als pH-Sonde

Intracellular pH probes is an emerging topic in the analysis of the role of protons play in the ongoing chemical processes within cells (e.g. in the respiratory chain) or in the diagnosis of functional disorders. In this study, a probe molecule based on the photoacid pyrenol was synthesized. Pyrenol derivatives can be used as a ratiometric pH probe or as an environmental probe. In the present thesis, a pyrenol derivative with a silane as a specific anchor group was synthesized, so that immobilization on glass surfaces could be realized. In addition, the immobilizable derivative of hydroxypyrene, was subsequently covalently embedded in silica nanoparticles. With the modified nanoparticles, both the properties of the probe molecule and the silica matrix were analyzed by steady-state and time-resolved fluorescence spectroscopy. There are several observations from the researchers. On one hand, a rigidly incorporation of the chromophore into the silica matrix could be confirmed. On the other hand, the embedded dye in core nanoparticles is accessible for protons. Therefore, the synthesized nanoparticles are suitable as an intracellular pH probe, which was demonstrated by in vitro cell experiments during this work.Intrazelluläre pH-Sonden sind von großem Interesse, um die Rolle von Protonen in ablaufenden chemischen Prozessen in Zellen näher zu analysieren (z.B. in der Atmungskette) oder um Fehlfunktionen bzw. Krankheiten zu diagnostizieren. In dieser Arbeit wurde ein Sondenmolekül synthetisiert, welches auf der Photosäure Pyrenol basiert. Pyrenolderivate können sowohl als ratiometrische pH-Sonde als auch als Umgebungssonde verwendet werden. In der vorliegenden Arbeit wurde ein Pyrenolderivat mit einem Silan als spezifische Ankergruppe dargestellt, sodass eine Immobilisierung auf Glasoberflächen realisiert wurde. Darüber hinaus wurde das hergestellte Sondenmolekül in Silica-Nanopartikel eingebaut. Nach Darstellung der modifizierten Nanopartikel wurden sowohl die Eigenschaften des Sondenmoleküls als auch der Silica-Matrix mit Hilfe von statistischer und zeitaufgelöster Fluoreszenzspektroskopie analysiert. Aus den Untersuchungen konnten mehrere Informationen gewonnen werden. Zum einen konnte ein fester Einbau des Chromophors in die Silica-Matrix bestätigt werden. Zum anderen wurde für den eingebundenen Farbstoff in Kern-Nanopartikel ein gutes Ansprechverhalten auf Protonen in der näheren Umgebung festgestellt. Die synthetisierten Nanopartikel eignen sich daher als intrazelluläre pH-Sonde, was im Rahmen dieser Arbeit durch in vitro Zellexperimente gezeigt wurde

Kinetics of Palladium(0)‐Allyl Interactions in the Tsuji‐Trost Reaction, derived from Single‐Molecule Fluorescence Microscopy

Single‐molecule (SM) chemistry is devoted to unravel reaction steps which are hidden in cuvette experiments. Controversies about the substrate activation during the Tsuji‐Trost deallylation motivated us to study, on the single‐molecule level, the kinetics of the catalyst precursor Pd(PPh3)4 with our recently designed two‐color fluorescent probes. Photochemical, metal‐free bypass reactions were found and taken into account by the combination of spectrally separated single‐molecule TIRF‐microscopy and state‐of‐the art analysis procedures. Unselective π‐complex formation (KD≈103 M−1) precedes the insertion of the active catalyst into the C−OR bond (RO−=leaving group), indicated by the lacking immediate change of fluorescence color. The formed intermediate then decomposes on a time scale of≥2 – 3 s to the deallylated product

Combining remote sensing, habitat suitability models and cellular automata to model the spread of the invasive shrub Ulex europaeus

Modeling the past or future spread patterns of invasive plant species is challenging and in an ideal case requires multi-temporal and spatially explicit data on the occurrences of the target species as well as information on the habitat suitability of the areas at risk of being invaded. Most studies either focus on modeling the habitat suitability of a given area for an invasive species or try to model the spreading behavior of an invasive species based on temporally or spatially limited occurrence data and some environmental variables. Here we suggest a workflow that combines habitat suitability maps, occurrence data from multiple time steps collected from remote sensing data, and cellular automata models to first reconstruct the spreading patterns of the invasive shrub Ulex europaeus on the island Chiloé in Chile and then make predictions for the future spread of the species. First, U. europaeus occurrences are derived for four time steps between 1988 and 2020 using remote sensing data and a supervised classification. The resulting occurrence data is combined with occurrence data of the native range of U. europaeus from the GBIF database and selected environmental variables to derive habitat suitability maps using Maxent. Then, cellular automata models are calibrated using the occurrence estimates of the four time steps, the suitability map, and some additional geo-layer containing information about soils and human infrastructure. Finally, a set of calibrated cellular automata models are used to predict the potential spread of U. europaeus for the years 2070 and 2100 using climate scenarios. All individual steps of the workflow where reference data was available led to sufficient results (supervised classifications Overall Accuracy > 0.97; Maxent AUC > 0.85; cellular automata Balanced Accuracy > 0.91) and the spatial patterns of the derived maps matched the experiences collected during the field surveys. Our model predictions suggest a continuous expansion of the maximal potential range of U. europaeus, particularly in the Eastern and Northern part of Chiloé Island. We deem the suggested workflow to be a good solution to combine the static habitat suitability information—representing the environmental constraints—with a temporally and spatially dynamic model representing the actual spreading behavior of the invasive species. The obtained understanding of spreading patterns and the information on areas identified to have a high invasion probability in the future can support land managers to plan prevention and mitigation measures

Mellom taushet og fare: Om kulturelle fortolkninger av psykiske problemer og forsøk på å skape ny mening

Artikkelen beskriver en forstdelse av psykiske problemer som inkluderer kunnskap om maktforhold mellom kjønnene. Psykiskesymptomer blir sett som kilde til informasjon om tabubelagte interessekonflikter og erfaringer med maktmisbruk. Terapeutiskforandring beskrives somforsøk på skape ny mening i den gamle historien, der målsettingen blir å skape verdighet for kvinnen.Dette innebærer å bekjempe sykeliggjørende fortolkninger av kvinners reaksjoner.The article describes an understanding of psychological problems that include the knowledge of power structures in the gender system. Psychological symptoms are seen as a source of information to tabooed conflicts of interest and experiences withpower abuse. Therapeutical change implies the creation of new meaning based on dignity by fighting the process of making women's reactions pathological

NIR-Emitting Gold Nanoclusters-Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

Gold nanocluster (AuNC) synthesis using a well-distinguished polymer for nanoparticle-mediated drug delivery paves the way for developing efficient theranostics based on pharmaceutically accepted materials. Gelatin-stabilized AuNCs are synthesized and modified by glutathione for tuning the emission spectra. Addition of silver ions enhances the fluorescence, reaching also high quantum yield (26.7%). A simplified model can be proposed describing the nanoclusters' properties-structure relationship based on X-ray photoelectron spectroscopy data and synthesis sequence. Furthermore, these modifications improve fluorescence stability toward pH changes and enzymatic degradation, offering different AuNCs for various applications. The impact of nanocluster formation on gelatin structure integrity is investigated by Fourier transform infrared spectrometry and matrix-assisted laser desorption/ionization time of flight mass spectroscopy, being important to further formulate gelatin nanoparticles (GNPs). The 218 nm-sized NPs show no cytotoxicity up to 600 µg mL-1 and are imaged in skin, as a challenging autofluorescent tissue, by confocal microscopy, when transcutaneously delivered using dissolving microneedles. Linear unmixing allows simultaneous imaging of AuNCs-GNPs and skin with accurate signal separation. This underlines the great potential for bioimaging of this system to better understand nanomaterials' behavior in tissue. Additionally, it is drug delivery system also potentially serving as a theranostic system

NIR‐Emitting Gold Nanoclusters–Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

Gold nanocluster (AuNC) synthesis using a well‐distinguished polymer for nanoparticle‐mediated drug delivery paves the way for developing efficient theranostics based on pharmaceutically accepted materials. Gelatin‐stabilized AuNCs are synthesized and modified by glutathione for tuning the emission spectra. Addition of silver ions enhances the fluorescence, reaching also high quantum yield (26.7%). A simplified model can be proposed describing the nanoclusters\u27 properties–structure relationship based on X‐ray photoelectron spectroscopy data and synthesis sequence. Furthermore, these modifications improve fluorescence stability toward pH changes and enzymatic degradation, offering different AuNCs for various applications. The impact of nanocluster formation on gelatin structure integrity is investigated by Fourier transform infrared spectrometry and matrix‐assisted laser desorption/ionization time of flight mass spectroscopy, being important to further formulate gelatin nanoparticles (GNPs). The 218 nm‐sized NPs show no cytotoxicity up to 600 µg mL−1 and are imaged in skin, as a challenging autofluorescent tissue, by confocal microscopy, when transcutaneously delivered using dissolving microneedles. Linear unmixing allows simultaneous imaging of AuNCs–GNPs and skin with accurate signal separation. This underlines the great potential for bioimaging of this system to better understand nanomaterials\u27 behavior in tissue. Additionally, it is drug delivery system also potentially serving as a theranostic system

Interdisciplinary: To Be or Not to Be? Working Across Disciplinary Boundaries in the Humanities (and Beyond)

This article introduces student readers to the realm of the interdisciplinary, with a primary focus on the humanities. We first introduce interdisciplinarity and other related terms as concepts. We then present eight specific examples, on which we illustrate interdisciplinary research. Finally, we address the question of when one should be interdisciplinary

Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension

We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for all drugs was 4–28 %. The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (Cmax) and minimum (Cmin) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at Cmin was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan. Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control.publishedVersio

The association of water carriage, water supply and sanitation usage with maternal and child health. A combined analysis of 49 Multiple Indicator Cluster Surveys from 41 countries

Background  Millions of people carry water home from off-plot sources each day and lack improved sanitation. Research on the health outcomes associated with water fetching is limited, and with usage of improved sanitation is inconclusive.  Objectives  To analyse the association of water fetching, unimproved water supplies, and usage of improved sanitation facilities with indicators of women’s and children’s health.  Methods  49 Multiple Indicator Cluster Surveys from 41 countries were merged, creating a data set of 2,740,855 people from 539,915 households. Multilevel, multivariable analyses were conducted, using logistic regression for binary outcomes, negative binomial regression for count data and ordinary linear regression for linear data. We adjusted for confounding factors and accounted for clustering at survey, cluster and household level.  Results  Compared to households in which no-one collects water, water fetching by any household member is associated with reduced odds of a woman giving birth in a health care facility (OR 0.88 to 0.90). Adults collecting water is associated with increased relative risk of childhood death (RR 1.04 to 1.05), children collecting water is associated with increased odds of diarrheal disease (OR 1.10 to 1.13) and women or girls collecting water is associated with reduced uptake of antenatal care (β-0.04 to -0.06) and increased odds of leaving a child under five alone for one or more hours, one or more days per week (OR 1.07 to 1.16). Unimproved water supply is associated with childhood diarhhoea (OR 1.05), but not child deaths, or growth scores. When the percentage of people using improved sanitation is more than 80% an association with reduced childhood death and stunting was observed, and when more than 60%, usage of improved sanitation was associated with reduction of diarhhoea and acute undernutrition.  Conclusion  Fetching water is associated with poorer maternal and child health outcomes, depending on who collects water. The percentage of people using improved sanitation seems to be more important than type of toilet facility, and must be high to observe an association with reduced child deaths and diarhhoea. Water access on premises, and near universal usage of improved sanitation, is associated with improvements to maternal and child health

Health care seeking behavior for diarrhea in children under 5 in rural Niger: results of a cross-sectional survey

Diarrhea remains the second leading cause of death in children under 5 years of age in sub-Saharan Africa. Health care seeking behavior for diarrhea varies by context and has important implications for developing appropriate care strategies and estimating burden of disease. The objective of this study was to determine the proportion of children under five with diarrhea who consulted at a health structure in order to identify the appropriate health care levels to set up surveillance of severe diarrheal diseases