R-vine Models for Spatial Time Series with an Application to Daily Mean Temperature

We introduce an extension of R-vine copula models for the purpose of spatial dependency modeling and model based prediction at unobserved locations. The newly derived spatial R-vine model combines the flexibility of vine copulas with the classical geostatistical idea of modeling spatial dependencies by means of the distances between the variable locations. In particular the model is able to capture non-Gaussian spatial dependencies. For the purpose of model development and as an illustration we consider daily mean temperature data observed at 54 monitoring stations in Germany. We identify a relationship between the vine copula parameters and the station distances and exploit it in order to reduce the huge number of parameters needed to parametrize a 54-dimensional R-vine model needed to fit the data. The new distance based model parametrization results in a distinct reduction in the number of parameters and makes parameter estimation and prediction at unobserved locations feasible. The prediction capabilities are validated using adequate scoring techniques, showing a better performance of the spatial R-vine copula model compared to a Gaussian spatial model.Comment: 28 pages, 10 figure

Shark Hunting: International Trade and the Imminent Extinction of Heterogeneous Species

This paper examines the unprecedented decimation of sharks. We develop a Ricardian Gordon-Schaefer model with a continuum of heterogeneous species which are subject to combined harvesting and perfect substitutability in consumption. The model implies that slow-growing species, surviving in autarky, will be driven to extinction in an open trade regime. In the empirical analysis, we show that the model is in line with observations of shark biology and the international shark market. In particular, the likelihood of extinction turns out to be significantly greater for shark species which are part of trade in shark fins and exhibit low intrinsic growth

Micro-inclusions in the EGRIP ice core identified with Raman-spectroscopy

Soluble and insoluble impurities play a crucial role regarding the deformability and thus the flow of polar ice. To better understand this interplay from a mechanistic point of view it is especially important to investigate the location and chemical composition of micro-inclusions (Stoll et al., 2021), which are among the most abundant impurities in polar ice. New results from a systematic analysis of micro-inclusions in Holocene ice from the East Greenland Ice Core Project (EGRIP), which has been drilled near the onset of the Northeast Greenland Ice Stream (NEGIS), offer unique insights into the dynamics of fast flowing ice over different scales, ranging from kilometres to micrometres. Investigating the small-scale properties of eleven samples from Holocene ice, i.e. the upper 1340 m of the EGRIP ice core, we mapped the locations of several thousand micro-inclusions inside the ice. The use of cryo-Raman spectroscopy allowed us to obtain a representative overview of the mineralogy of these inclusions in the ice without the risk of contamination. We identified a variety of Raman spectra, mainly from sulphates (dominated by gypsum) and terrestrial dust, such as quartz, mica and feldspar. The observed mineralogy changes with depth and EGRIP Holocene ice can be categorised in two different depth regimes, i.e. the upper (100-900 m) and lower (900-1340 m) regimes, depending on their mineralogy. Furthermore, micro- inclusions show certain spatial patterns, such as clustering or layering, which are partly related to their mineralogy. We thus conclude that Greenlandic Holocene ice has a broader, and more variable, mineralogy than previously reported and that chemical reactions might take place within the ice sheet, possibly altering the paleo-climate record. Our approach further demonstrates the added value of systematic, combined high-resolution impurity and microstructural studies, and the importance of considering different spatial scales and is thus another step towards a more holistic understanding of impurities in ice

Microstructure, micro-inclusions, and mineralogy along the EGRIP (East Greenland Ice Core Project) ice core – Part 2: Implications for palaeo-mineralogy

Impurities in polar ice do not only allow the re- construction of past atmospheric aerosol concentrations but also influence the physical properties of the ice. However, the localisation of impurities inside the microstructure is still un- der debate and little is known about the mineralogy of solid inclusions. In particular, the general mineralogical diversity throughout an ice core and the specific distribution inside the microstructure is poorly investigated; the impact of the mineralogy on the localisation of inclusions and other pro- cesses is thus hardly known. We use dust particle concen- tration, optical microscopy, and cryo-Raman spectroscopy to systematically locate and analyse the mineralogy of micro- inclusions in situ inside 11 solid ice samples from the up- per 1340 m of the East Greenland Ice Core Project ice core. Micro-inclusions are more variable in mineralogy than pre- viously observed and are mainly composed of mineral dust (quartz, mica, and feldspar) and sulfates (mainly gypsum). Inclusions of the same composition tend to cluster, but clus- tering frequency and mineralogy changes with depth. A va- riety of sulfates dominate the upper 900 m, while gypsum is the only sulfate in deeper samples, which however contain more mineral dust, nitrates, and dolomite. The analysed part of the core can thus be divided into two depth regimes of different mineralogy, and to a lesser degree of spatial distri- bution, which could originate from different chemical reac- tions in the ice or large-scale changes in ice cover in north- east Greenland during the mid-Holocene. The complexity of impurity mineralogy on the metre scale and centimetre scale in polar ice is still underestimated, and new methodological approaches are necessary to establish a comprehensive un- derstanding of the role of impurities. Our results show that applying new methods to the mineralogy in ice cores and recognising its complexity, as well as the importance for lo- calisation studies, open new avenues for understanding the role of impurities in ice cores

Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells

Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimer’s disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimer’s disease

Vitamin D and Its Analogues: From Differences in Molecular Mechanisms to Potential Benefits of Adapted Use in the Treatment of Alzheimer’s Disease

Lifestyle habits and insufficient sunlight exposure lead to a high prevalence of vitamin D hypovitaminosis, especially in the elderly. Recent studies suggest that in central Europe more than 50% of people over 60 years are not sufficiently supplied with vitamin D. Since vitamin D hypovitaminosis is associated with many diseases, such as Alzheimer’s disease (AD), vitamin D supplementation seems to be particularly useful for this vulnerable age population. Importantly, in addition to vitamin D, several analogues are known and used for different medical purposes. These vitamin D analogues differ not only in their pharmacokinetics and binding affinity to the vitamin D receptor, but also in their potential side effects. Here, we discuss these aspects, especially those of the commonly used vitamin D analogues alfacalcidol, paricalcitol, doxercalciferol, tacalcitol, calcipotriol, and eldecalcitol. In addition to their pleiotropic effects on mechanisms relevant to AD, potential effects of vitamin D analogues on comorbidities common in the context of geriatric diseases are summarized. AD is defined as a complex neurodegenerative disease of the central nervous system and is commonly represented in the elderly population. It is usually caused by extracellular accumulation of amyloidogenic plaques, consisting of amyloid (Aβ) peptides. Furthermore, the formation of intracellular neurofibrillary tangles involving hyperphosphorylated tau proteins contributes to the pathology of AD. In conclusion, this review emphasizes the importance of an adequate vitamin D supply and discusses the specifics of administering various vitamin D analogues compared with vitamin D in geriatric patients, especially those suffering from AD

Duplex Structures in the EastGRIP Ice Core - the Loss of Stratigraphic Integrity

The EastGRIP ice core is drilled through the Northeast Greenland Ice Stream, which has a surface velocity of 55 m/yr&amp;#160;towards NNE at the drill site. Deriving a better understanding of internal deformation and the rheology within an ice stream is crucial for ice flow models and projections of future solid ice discharge. We use the line scanner to make the stratigraphy visible and document disturbances in the layering in the depth region from 1375 to 2120 m covering a large part of the Glacial Period. Disturbances are visible in cuts perpendicular to the ice flow direction, and not in cuts parallel to flow. Between these two extremes, we have a gradual change in type and amount of disturbances. As with all other ice cores, the ice in the EastGRIP ice core is thinned vertically. Due to the advanced thinning of layers, it is clear that the visible structures are not the remnants of surface features, such as sastrugi. &amp;#160;However, the disturbances, or deformation structures, are the result of strain caused by the stress field at the EastGRIP site, which is described by a compressional component perpendicular to and an extensional component parallel to the ice flow direction. In most samples cut perpendicular to ice flow, i.e. with the compressional setting visible, we find structures, very similar to geological duplex structures. We identify duplex structures extending the width of the core by the sudden change of layer tilt within one bag at a time. Duplex structures are confined by layer parallel shear zones, with tilted layers in between them. The small-scale shear zones only become evident due to the deformation they cause and can extend well beyond these visible structures. We furthermore suggest, that shear zones are present parallel to layering, but do not show up, as a lateral displacement of layers, does not disrupt the vertical profiles. We discuss one example, from a depth of 1651 m (26 ky b2k), in detail. We further investigate approx. 30 m of chemical CFA data, mainly NH4+ and Ca++, from the same depth. We find peaks that double, in both the visual stratigraphy as well as the CFA data. These may be a result of the duplex structures that stack the stratigraphy and have the potential to disturb the climate record. Our results display the importance of understanding internal deformation when interpreting the climate record.</jats:p

Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells

Due to a worldwide increase in obesity and metabolic disorders such as type 2 diabetes, synthetic sweeteners such as aspartame are frequently used to substitute sugar in the diet. Possible uncertainties regarding aspartame’s ability to induce oxidative stress, amongst others, has led to the recommendation of a daily maximum dose of 40 to 50 mg per kg. To date, little is known about the effects of this non-nutritive sweetener on cellular lipid homeostasis, which, besides elevated oxidative stress, plays an important role in the pathogenesis of various diseases, including neurodegenerative diseases such as Alzheimer’s disease. In the present study, treatment of the human neuroblastoma cell line SH-SY5Y with aspartame (271.7 µM) or its three metabolites (aspartic acid, phenylalanine, and methanol (271.7 µM)), generated after digestion of aspartame in the human intestinal tract, resulted in significantly elevated oxidative stress associated with mitochondrial damage, which was illustrated with reduced cardiolipin levels, increased gene expression of SOD1/2, PINK1, and FIS1, and an increase in APF fluorescence. In addition, treatment of SH-SY5Y cells with aspartame or aspartame metabolites led to a significant increase in triacylglycerides and phospholipids, especially phosphatidylcholines and phosphatidylethanolamines, accompanied by an accumulation of lipid droplets inside neuronal cells. Due to these lipid-mediating properties, the use of aspartame as a sugar substitute should be reconsidered and the effects of aspartame on the brain metabolism should be addressed in vivo