Parallel Multi-Hypothesis Algorithm for Criticality Estimation in Traffic and Collision Avoidance

Due to the current developments towards autonomous driving and vehicle active safety, there is an increasing necessity for algorithms that are able to perform complex criticality predictions in real-time. Being able to process multi-object traffic scenarios aids the implementation of a variety of automotive applications such as driver assistance systems for collision prevention and mitigation as well as fall-back systems for autonomous vehicles. We present a fully model-based algorithm with a parallelizable architecture. The proposed algorithm can evaluate the criticality of complex, multi-modal (vehicles and pedestrians) traffic scenarios by simulating millions of trajectory combinations and detecting collisions between objects. The algorithm is able to estimate upcoming criticality at very early stages, demonstrating its potential for vehicle safety-systems and autonomous driving applications. An implementation on an embedded system in a test vehicle proves in a prototypical manner the compatibility of the algorithm with the hardware possibilities of modern cars. For a complex traffic scenario with 11 dynamic objects, more than 86 million pose combinations are evaluated in 21 ms on the GPU of a Drive PX~2

Latest Pleistocene and Holocene Floodplain Evolution in Central Europe—Insights from the Upper Unstrut Catchment (NW-Thuringia/Germany)

The upper Unstrut River is located in Germany at the modern Central European climate boundary of Cfb and Dfb climate. The river drains a loess landscape, which has experienced important environmental changes throughout the last 12,000 years. To evaluate the impacts of these changes on floodplain evolution, a multi-proxy research program, consisting of 2D electrical resistivity tomography profiling (ERT), vibracoring, and sedimentological investigations, 14C and OSL dating were applied. From base to top the investigations the following fluvial deposits were revealed: (1) gravels embedded in a fine-grained sediment matrix (interpreted as fluvial bedload deposits); (2) silty sediment with pedogenic features (interpreted as overbank floodplain deposits); (3) peat and tufa deposits (interpreted as wetland deposits) intercalated by pedogenetically influenced silty sediments (interpreted as overbank deposits); (4) humic silty sediment with some pedogenic features (interpreted as overbank floodplain deposits); and (5) silty sediments (interpreted as overbank deposits). Radiocarbon and luminescence dates yielded the following periods for sediment formation: (1) Younger Dryas to Preboreal period (around 11.6 cal ka BP); (2) Preboreal to early Atlantic period (approx. 11.6 to 7.0 cal ka BP); (3) early Atlantic to late Subboreal period (approx. 7.3 to 3.4 cal ka BP); (4) late Subboreal to early Subatlantic period (2.9 to 2.3 cal ka BP); and (5) late Subatlantic period (approx. 1.0 to 0.6 cal ka BP). The results suggest that floodplain development during the latest Pleistocene and early Holocene (approx. 11.6 to 7.0 cal ka BP) was considerably controlled by climatic conditions and short-term climate variabilities, which caused gravel deposition and overbank sedimentation. Afterwards floodplain conditions varied between rather stable (peat and tufa development, initial soil formation) and active periods (deposition of overbank fines)

Geoarchaeological studies on Roman time harbour sediments in Cologne — comparison of different OSL dating techniques

Due to the construction of a new North-South subway in Cologne, Roman time harbour sediments were exposed and were sampled for luminescence dating. A very good independent age control was given by the precise knowledge of the chronology of Roman activity and by radiocarbon ages of charcoal samples. Hence, different methodological approaches within luminescence dating were applied for Holocene heterogeneously bleached fluvial samples and were compared to the known ages. For one sample, optically stimulated luminescence (OSL) dating was applied to coarse-grained quartz using a single aliquot regenerative-dose (SAR) protocol. After De-measurements, dif-ferent statistical approaches were tested (i.e. arithmetic mean, median, minimum age model, finite mixture model, leading edge method and the Fuchs and Lang approach). It is demonstrated that the Fuchs and Lang approach along with the leading edge method yielded the best matching OSL ages with respect to the known ages. For the other sample which showed feldspar contamination within the quartz signal, the post-IR blue stimulated luminescence (double SAR protocol) was measured in three different ways to calculate the De-value: with continuous wave (CW) stimulation with an IR-bleach at 50°C and at 225°C for 100 s prior to the OSL, and pulsed OSL (POSL). It was demonstrated that the IR-stimulation at 225°C has very good potential to remove the feldspar signal contribution as well as pulsed OSL, but the former might deplete parts of the quartz OSL signal. © 2011 Silesian University of Technology, Gliwice, Poland. All rights reserved

New age constraints for the Saalian glaciation in northern central Europe: Implications for the extent of ice sheets and related proglacial lake systems

A comprehensive palaeogeographic reconstruction of ice sheets and related proglacial lake systems for the older Saalian glaciation in northern central Europe is presented, which is based on the integration of palaeo-ice flow data, till provenance, facies analysis, geomorphology and new luminescence ages of ice-marginal deposits. Three major ice advances with different ice-advance directions and source areas are indicated by palaeo-ice flow directions and till provenance. The first ice advance was characterised by a southwards directed ice flow and a dominance of clasts derived from southern Sweden. The second ice advance was initially characterised by an ice flow towards the southwest. Clasts are mainly derived from southern and central Sweden. The latest stage in the study area (third ice advance) was characterised by ice streaming (Hondsrug ice stream) in the west and a re-advance in the east. Clasts of this stage are mainly derived from eastern Fennoscandia. Numerical ages for the first ice advance are sparse, but may indicate a correlation with MIS 8 or early MIS 6. New pIRIR290 luminescence ages of ice-marginal deposits attributed to the second ice advance range from 175 ± 10 to 156 ± 24 ka and correlate with MIS 6. The ice sheets repeatedly blocked the main river-drainage pathways and led to the formation of extensive ice-dammed lakes. The formation of proglacial lakes was mainly controlled by ice-damming of river valleys and major bedrock spillways; therefore the lake levels and extends were very similar throughout the repeated ice advances. During deglaciation the lakes commonly increased in size and eventually drained successively towards the west and northwest into the Lower Rhine Embayment and the North Sea. Catastrophic lake-drainage events occurred when large overspill channels were suddenly opened. Ice-streaming at the end of the older Saalian glaciation was probably triggered by major lake-drainage events

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

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

Approximately 90% of the elderly population in the western countries has at least a mild to moderate vitamin D hypovitaminosis. Besides the well-known function of vitamin D in calcium homeostasis, it has been recently found that several enzymes and receptors involved in its homeostasis are expressed in the nervous system and brain suggesting also an important role in the brain homeostasis. Interestingly, epidemiological and clinical studies found reduced vitamin D level associated with an increased risk of several neurodegenerative disorders. In this chapter, we focus on a potential link between vitamin D and Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, prion disease, and motor neuron disease. Epidemiological studies were summarized, an overview of the known potential underlying pathomolecular mechanisms are given, and results from clinical studies dealing with vitamin D supplementation were presented. As an outlook, recent literature suggesting an impact of vitamin D on autism spectrum disease, depression, and schizophrenia are briefly discussed. In conclusion, the identification of an abundant vitamin D metabolism in the brain and the tight link between the increasing number of several neurological and mental disorders emphasize the need of further research making a clear recommendation of the intake and supplementation of vitamin D in a growing elderly population

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

Host‐Guest Chemistry of Truncated Tetrahedral Imine Cages with Ammonium Ions

Three shape-persistent [4+4] imine cages with truncated tetrahedral geometry with different window sizes were studied as hosts for the encapsulation of tetra-n-alkylammonium salts of various bulkiness. In various solvents the cages behave differently. For instance, in dichloromethane the cage with smallest window size takes up NEt$_{4}$t$^{+}$ but not NMe$_{4}$t$^{+}$, which is in contrast to the two cages with larger windows hosting both ions. To find out the reason for this, kinetic experiments were carried out to determine the velocity of uptake but also to deduce the activation barriers for these processes. To support the experimental results, calculations for the guest uptakes have been performed by molecular mechanics’ simulations. Finally, the complexation of pharmaceutical interested compounds, such as acetylcholine, muscarine or denatonium have been determined by NMR experiments

Methylxanthines and Neurodegenerative Diseases: An Update

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases

Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class