Application of Complexity Measures to Stratospheric Dynamics

This thesis examines the utility of mathematical complexity measures for the analysis of stratospheric dynamics. Through theoretical considerations and tests with artificial data sets, e.g., the iteration of the logistic map, suitable parameters are determined for the application of the statistical entropy measures sample entropy (SE) and Rényi entropy (RE) to methane (a long-lived stratospheric tracer) data from simulations of the SOCOL chemistry-climate model. The SE is shown to be useful for quantifying the variability of recurring patterns in a time series and is able to identify tropical patterns similar to those reported by previous studies of the ``tropical pipe'' region. However, the SE is found to be unsuitable for use in polar regions, due to the non-stationarity of the methane data at extra-tropical latitudes. It is concluded that the SE cannot be used to analyse climate complexity on a global scale. The focus is turned to the RE, which is a complexity measure of probability distribution functions (PDFs). Using the second order RE and a normalisation factor, zonal PDFs of ten consecutive days of methane data are created with a Bayesian optimal binning technique. From these, the RE is calculated for every day (moving 10-day window). The results indicate that the RE is a promising tool for identifying stratospheric mixing barriers. In Southern Hemisphere winter and early spring, RE produces patterns similar to those found in other studies of stratospheric mixing. High values of RE are found to be indicative of the strong fluctuations in tracer distributions associated with relatively unmixed air in general, and with gradients in the vicinity of mixing barriers, in particular. Lower values suggest more thoroughly mixed air masses. The analysis is extended to eleven years of model data. Realistic inter-annual variability of some of the RE structures is observed, particularly in the Southern Hemisphere. By calculating a climatological mean of the RE for this period, additional mixing patterns are identified in the Northern Hemisphere. The validity of the RE analysis and its interpretation is underlined by showing that qualitatively similar patterns can be seen when using observational satellite data of a different tracer. Compared to previous techniques, the RE has the advantage that it requires significantly less computational effort, as it can be used to derive dynamical information from model or measurement tracer data without relying on any additional input such as wind fields. The results presented in this thesis strongly suggest that the RE is a useful new metric for analysing stratospheric mixing and its variability from climate model data. Furthermore, it is shown that the RE measure is very robust with respect to data gaps, which makes it ideal for application to observations. Hence, using the RE for comparing observations of tracer distributions with those from model simulations potentially presents a novel approach for analysing mixing in the stratosphere

Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD

BACKGROUND: Activation of fibroblast growth factor receptor (FGFR)-dependent signalling by FGF23 may contribute to the complex pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD, but its ability to treat and reverse established LVH is unknown. METHODS: CKD was induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function was determined by urine and blood analyses. Left ventricular (LV) structure and function were determined by echocardiography, histopathology, staining for myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression profiles by real-time PCR. RESULTS: Two weeks after inducing CKD by 5/6 nephrectomy, rats manifested higher (mean ± SEM) systolic blood pressure (208 ± 4 versus 139 ± 3 mmHg; P < 0.01), serum FGF23 levels (1023 ± 225 versus 199 ± 9 pg/mL; P < 0.01) and LV mass (292 ± 9 versus 220 ± 3 mg; P < 0.01) when compared with sham-operated animals. Thereafter, 3 weeks of treatment with PD173074 compared with vehicle did not significantly change blood pressure, kidney function or metabolic parameters, but significantly reduced LV mass (230 ± 14 versus 341 ± 33 mg; P < 0.01), myocardial fibrosis (2.5 ± 0.7 versus 5.4 ± 0.95% staining/field; P < 0.01) and cardiac expression of genes associated with pathological LVH, while significantly increasing ejection fraction (18 versus 2.5% post-treatment increase; P < 0.05). CONCLUSIONS: FGFR blockade improved cardiac structure and function in 5/6 nephrectomy rats with previously established LVH. These data support FGFR activation as a potentially modifiable, blood pressure-independent molecular mechanism of LVH in CKD

Ein Plädoyer für die Entwicklung eines multidimensionalen Ordnungsrahmens zur hybriden Wertschöpfung

Mit Ordnungsrahmen lassen sich hoch aggregierte Überblicke über die wesentlichen Funktionsbereiche einer Domäne darstellen. Der Beitrag regt die Entwicklung eines Ordnungsrahmens für die hybride Wertschöpfung an. Mit der Konstruktion des Ordnungsrahmens wird die Grundlage für einen strukturierten Überblick über die für die hybride Wertschöpfung bereits entwickelten bzw. zukünftig zu entwickelnden Artefakte bereitgestellt. Damit erleichtert die Übersicht einerseits die Identifizierung von Weiterentwicklungspotenzialen im Rahmen einer artefaktschaffenden Forschung und bietet andererseits einen Gesamtüberblick über in der unternehmerischen Praxis einsetzbare Artefakte. Als Ausgangspunkt für weitere Arbeiten zum Aufbau des Ordnungsrahmens wird ein Vorschlag zu dessen inhaltlicher Gestaltung präsentiert. Der vorgestellte Ordnungsrahmen wird evaluiert, indem er zur Strukturierung von in Expertenbefragungen erhobenen Artefakten der hybriden Wertschöpfung herangezogen wird

FGF23/FGFR4-mediated left ventricular hypertrophy is reversible

Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH

Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy

Chronic kidney disease (CKD) is a worldwide public health threat that increases risk of death due to cardiovascular complications, including left ventricular hypertrophy (LVH). Novel therapeutic targets are needed to design treatments to alleviate the cardiovascular burden of CKD. Previously, we demonstrated that circulating concentrations of fibroblast growth factor (FGF) 23 rise progressively in CKD and induce LVH through an unknown FGF receptor (FGFR)-dependent mechanism. Here, we report that FGF23 exclusively activates FGFR4 on cardiac myocytes to stimulate phospholipase C gamma/calcineurin/nuclear factor of activated T cell signaling. A specific FGFR4-blocking antibody inhibits FGF23-induced hypertrophy of isolated cardiac myocytes and attenuates LVH in rats with CKD. Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas knockin mice carrying an FGFR4 gain-of-function mutation spontaneously develop LVH. Thus, FGF23 promotes LVH by activating FGFR4, thereby establishing FGFR4 as a pharmacological target for reducing cardiovascular risk in CKD