Origin and evolution of Upper Triassic to Miocene clay-mineral associations from the eastern Algarve of Portugal

XRD-analyses of pelitic deposits of Upper Jurassic to Miocene age occuring in the eastern Algarve (Portugal), give evidence of the occurrence of detrital clay minerals of continental origin as well as of conspicuous neoformations of marine provenance. The vertical succession of clay-mineral associations indicates the existence of three distinctive evolutionary cycles which are thought to reflect tectonically controlled transgressive-regressive events

Development of colloidal drug delivery systems for the stabilization of hyperforin

Ziel dieser Arbeit war es, für das schwer wasserlösliche und chemisch instabile Hyperforin-Molekül eine geeignete kolloidale Formulierung auf der Basis von unterschiedlichen Arzneistoffträgersystemen zu entwickeln. Dafür wurde das seit Anfang der 2000er Jahre bekannte und vergleichsweise stabile Dicyclohexylammoniumsalz (HYP-DCHA) verwendet. Als Voraussetzung für die Einarbeitung von HYP-DCHA in kolloidale Arzneistoffträgersysteme konnte in dieser Arbeit gezeigt werden, dass eine ethanolische HYP-DCHA-Lösung bei 8 °C für mindestens 6 Wochen und bei 60 °C für mindestens 4 Stunden stabil ist.Als erstes Arzneistoffträgersystem wurden Polymernanopartikel aus Bovinem Serumalbumin (BSA) untersucht. Die Herstellung erfolgte durch Desolvatation und die anschließende Stabilisierung durch thermische Quervernetzung. Die daraus resultierenden Albumin-Nanopartikel (ANP) waren unter kontrollierten Bedingungen in einer engen und über mindestens 3 Wochen stabilen Partikelgrößenverteilung produzierbar. Über einen Zeitraum von 2 Wochen konnten die ANP 92 % des HYP-DCHA einer HYP-DCHA-Beladung mit 1 μmol/l stabilisieren. Als lipidhaltige Arzneistoffträgersysteme wurden Suspensionen aus festen Lipidnanopartikeln (solid lipid nanoparticles, SLN) und Nanoemulsionen (NE) untersucht. Die Herstellung der Nanopartikel erfolgte in einer Mikrokanalhochdruckemulgieranlage. Die verwendeten Prozessparameter wurden mit einer statistischen Versuchsplanung (Design of Experiments, DoE) in einem Central Composite Inscribed (CCI) Modell optimiert. Damit ließen sich die Parameter für eine mittlere Partikelgröße von ca. 120 nm berechnen und reproduzierbar herstellen. Für die Herstellung der SLN-Formulierungen in der Mikrokanalhochdruckemulgieranlage müssen diese auf 70 °C erwärmt werden. Diese erhöhte Temperatur führte innerhalb von wenigen Minuten zu einer Degradierung des in den Formulierungen enthaltenen HYP-DCHA. Das Lipid der Nanoemulsionen ist bei Raumtemperatur flüssig, weshalb zur Herstellung die Kalt-Homogenisation verwendet wurde. Aber erst durch eine passive Beladungsmethode und den Zusatz einer Albuminlösung ist es gelungen, eine kolloidale HYP-DCHA-Formulierung auf Basis von Nanoemulsionen zu entwickeln, in der das empfindliche HYP-DCHA für über 2 Wochen stabil ist. Für eine mögliche kutane Applikation der HYP-DCHA-Formulierungen wurden diese abschließend in einer in-vitro 2D-Kultivierung von Keratinozyten-(HaCaT)-Zellen untersucht.The aim of this work was to develop a suitable colloidal formulation for the poorly water soluble and chemically unstable hyperforin molecule on the basis of different drug delivery systems. For this purpose, the comparatively stable dicyclohexylammonium salt (HYP-DCHA) known from the 2000s years is used. As a prerequisite for working with HYP-DCHA in colloidal drug delivery systems, it could be shown in this work that an ethanolic solution from the HYP-DCHA is stable for at least 6 weeks with 8 °C and for at least 4 hours with 60 °C. The first drug delivery system to be investigated were polymer nanoparticles of bovine serum albumin (BSA). They were produced by desolvation and then stabilized by thermal crosslinking. The resulting albumin nanoparticles (ANP) could be produced under controlled conditions in a narrow and stable particle size distribution for at least 3 weeks. Over a period of two weeks, the ANP stabilized 92 % of the HYP-DCHA (loaded with 1 μmol/l HYP- DCHA). Suspensions of solid lipid nanoparticles (SLN) and nanoemulsions (NE) were investigated as lipid-containing drug delivery systems. The nanoparticles were produced in a customized microchannel high pressure homogenization device. The used process parameters were optimized with a statistical Design of Experiments (DoE) in a Central Composite Inscribed (CCI) model. Thus, the parameters for an average particle size of approximately 120 nm can be calculated and reproducibly produced. The SLN formulations must be heated to 70 °C before they could be homogenizated in the microchannel high pressure homogenization device. The elevated temperature led to a degradation of the HYP-DCHA contained in the formulations within a few minutes. The lipid of the nanoemulsions is liquid at room temperature, which is why cold homogenization was used to produce them. It has also been shown that dissolved native bovine serum albumin has a stabilizing property for HYP-DCHA. By adding an albumin solution to the NE formulations, it was possible to stabilize the HYP-DCHA over a period of 31 days. A loading with almost 100 % of the used HYP-DCHA could only be achieved by a passive loading method. Thus, it has been possible to develop a colloidal HYP-DCHA formulation, in which the sensitive HYP-DCHA is stable for over 2 weeks. For a potential cutaneous application of the HYP-DCHA formulations, these were finally examined in an in vitro 2D cultivation of keratinocyte (HaCaT) cells

Low Mortality in Tall Tropical Trees

The dynamics of the tallest trees in tropical forests are of special interest due to their carbon content, canopy dominance, and the large canopy gaps created when they die. Known ecological mechanisms that may influence tall tree survival lead to conflicting predictions. Hydraulic stress and exposure to high winds and desiccation should increase death rates, yet the tallest trees have the greatest access to light and escape damage caused by falling boles and branches. The uncertainty in tall tree mortality rates has been difficult to address due to their low density, which makes mortality rates challenging to estimate accurately. Here, we use a combination of LiDAR remote sensing and field measurements to show that the mortality rate over 8.5 years among individuals \u3e40 m tall in 444 ha of lowland Neotropical rain forest was 1.2% per year, less than half the landscape-scale average for all canopy trees (2.7% per year). The low mortality is likely explained by species-specific traits that decrease the mortality risk and/or ecological advantages of height that outweigh the risks. Regardless of the mechanisms, the low mortality rate has important implications for tropical forest carbon budgets, as we estimated that a single tall individual represents 2–11% of total live aboveground carbon stocks per hectare. Our findings suggest that height-specific dynamics may be surprisingly different from traditional diameter-specific dynamics, emphasizing the importance of extending ecological studies to investigate the role of tree height in forest dynamics

Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019

This paper studies the features of metabolic parameters, diabetic complications and drug therapy of a single-centre cohort of patients with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) in secondary care and tertiary care over a 15-year period. Methods: Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care ( n = 5571) or tertiary care ( n = 2001) were included. Statistical analyses were performed using linear mixed models. Results: Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care ( p < 0.001). Patients in secondary care consistently showed good glycaemic control, while patients in tertiary care showed inadequate glycaemic control. All four cross-sectional cohorts showed a significant increase in the prevalence of nephropathy over time and three out of four cohorts (T1DM and T2DM in secondary care and T2DM in tertiary care) showed an increase in the prevalence of neuropathy (all p < 0.001). The incidence of severe hypoglycaemia was consistently low. The use of insulin pumps and insulin analogues in the therapy of T1DM increased significantly. Conclusions: The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care

Data management routines for reproducible research using the G-Node Python Client library

Structured, efficient, and secure storage of experimental data and associated meta-information constitutes one of the most pressing technical challenges in modern neuroscience, and does so particularly in electrophysiology. The German INCF Node aims to provide open-source solutions for this domain that support the scientific data management and analysis workflow, and thus facilitate future data access and reproducible research. G-Node provides a data management system, accessible through an application interface, that is based on a combination of standardized data representation and flexible data annotation to account for the variety of experimental paradigms in electrophysiology. The G-Node Python Library exposes these services to the Python environment, enabling researchers to organize and access their experimental data using their familiar tools while gaining the advantages that a centralized storage entails. The library provides powerful query features, including data slicing and selection by metadata, as well as fine-grained permission control for collaboration and data sharing. Here we demonstrate key actions in working with experimental neuroscience data, such as building a metadata structure, organizing recorded data in datasets, annotating data, or selecting data regions of interest, that can be automated to large degree using the library. Compliant with existing de-facto standards, the G-Node Python Library is compatible with many Python tools in the field of neurophysiology and thus enables seamless integration of data organization into the scientific data workflow

Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography

Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at ≥3.5 µmol/L Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine ≥3.5 µmol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography