Practical implementation of nonlinear time series methods: The TISEAN package

Nonlinear time series analysis is becoming a more and more reliable tool for the study of complicated dynamics from measurements. The concept of low-dimensional chaos has proven to be fruitful in the understanding of many complex phenomena despite the fact that very few natural systems have actually been found to be low dimensional deterministic in the sense of the theory. In order to evaluate the long term usefulness of the nonlinear time series approach as inspired by chaos theory, it will be important that the corresponding methods become more widely accessible. This paper, while not a proper review on nonlinear time series analysis, tries to make a contribution to this process by describing the actual implementation of the algorithms, and their proper usage. Most of the methods require the choice of certain parameters for each specific time series application. We will try to give guidance in this respect. The scope and selection of topics in this article, as well as the implementational choices that have been made, correspond to the contents of the software package TISEAN which is publicly available from http://www.mpipks-dresden.mpg.de/~tisean . In fact, this paper can be seen as an extended manual for the TISEAN programs. It fills the gap between the technical documentation and the existing literature, providing the necessary entry points for a more thorough study of the theoretical background.Comment: 27 pages, 21 figures, downloadable software at http://www.mpipks-dresden.mpg.de/~tisea

Fast multi-core based multimodal registration of 2D cross-sections and 3D datasets

<p>Abstract</p> <p>Background</p> <p>Solving bioinformatics tasks often requires extensive computational power. Recent trends in processor architecture combine multiple cores into a single chip to improve overall performance. The Cell Broadband Engine (CBE), a heterogeneous multi-core processor, provides power-efficient and cost-effective high-performance computing. One application area is image analysis and visualisation, in particular registration of 2D cross-sections into 3D image datasets. Such techniques can be used to put different image modalities into spatial correspondence, for example, 2D images of histological cuts into morphological 3D frameworks.</p> <p>Results</p> <p>We evaluate the CBE-driven PlayStation 3 as a high performance, cost-effective computing platform by adapting a multimodal alignment procedure to several characteristic hardware properties. The optimisations are based on partitioning, vectorisation, branch reducing and loop unrolling techniques with special attention to 32-bit multiplies and limited local storage on the computing units. We show how a typical image analysis and visualisation problem, the multimodal registration of 2D cross-sections and 3D datasets, benefits from the multi-core based implementation of the alignment algorithm. We discuss several CBE-based optimisation methods and compare our results to standard solutions. More information and the source code are available from <url>http://cbe.ipk-gatersleben.de</url>.</p> <p>Conclusions</p> <p>The results demonstrate that the CBE processor in a PlayStation 3 accelerates computational intensive multimodal registration, which is of great importance in biological/medical image processing. The PlayStation 3 as a low cost CBE-based platform offers an efficient option to conventional hardware to solve computational problems in image processing and bioinformatics.</p

ER localized bestrophin1 activates Ca2+ dependent ion channels TMEM16A and SK4

Bestrophins form Ca2+ activated Cl- channels and regulate intercellular Ca2+ signaling1. We demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it physically interacts with stromal interacting molecule 1 (Stim1), the ER-Ca2+ sensor2,3. Intracellular Ca2+ transients in HEK293 cells elicited by stimulation of purinergic P2Y2-receptors were augmented but more transient after expression of hBest1, in contrast to dominant negative hBest1-R218C, which attenuated Ca2+ increase. The p21-activated protein kinase Pak2 was found to phosphorylate hBest1, thereby enhancing Ca2+ signaling and activation of Ca2+ dependent Cl- (TMEM16A)4 and K+ (SK4)5 channels. Lack of bestrophin 1 expression in respiratory epithelial cells of mBest1 knockout mice caused expansion of ER cisterns and induced Ca2+ deposits. We propose that hBest1 is important for Ca2+ handling of the ER store, probably by controlling the function of Stim1 and by acting as a counter-ion channel to balance transient membrane potentials occurring through inositol trisphosphate (IP3) induced Ca2+ release and refill of the ER-Ca2+ store. Thus bestrophin 1 controls activation of Ca2+ dependent ion channels by regulation of compartmentalized Ca2+ signaling

Mitoxantrone Loaded Superparamagnetic Nanoparticles for Drug Targeting: A Versatile and Sensitive Method for Quantification of Drug Enrichment in Rabbit Tissues Using HPLC-UV

In medicine, superparamagnetic nanoparticles bound to chemotherapeutics are currently investigated for their feasibility in local tumor therapy. After intraarterial application, these particles can be accumulated in the targeted area by an external magnetic field to increase the drug concentration in the region of interest (Magnetic-Drug-Targeting). We here present an analytical method (HPLC-UV), to detect pure or ferrofluid-bound mitoxantrone in a complex matrix even in trace amounts in order to perform biodistribution studies. Mitoxantrone could be extracted in high yields from different tissues. Recovery of mitoxantrone in liver tissue (5000 ng/g) was 76 ± 2%. The limit of quantification of mitoxantrone standard was 10 ng/mL ±12%. Validation criteria such as linearity, precision, and stability were evaluated in ranges achieving the FDA requirements. As shown for pilot samples, biodistribution studies can easily be performed after application of pure or ferrofluid-bound mitoxantrone

Herausforderungen und Entwicklungsperspektiven des Steuersystems

We analyze the development perspectives of Germany’s and Austria’s tax systems, considering the massive economic and societal challenges of digitalization, economic inequality and climate change. Digitalization complicates taxation due to decreasing physical presence and increasing international mobility of tax bases. Since labor is internationally less mobile, taxes on labor income will remain an integral part of both countries’ tax systems. This is also true for the value added tax that taxes local consumption, which is internationally hardly mobile. In contrast, taxes on mobile corporate profits will tend to lose importance as long as tax competition is not effectively curbed by international co-operation. Therefore, taxation of corporate profits should be oriented to the individual final beneficial owners who tend to be largely immobile. Due to high compliance costs and possibilities for international tax avoidance, the wealth tax is inappropriate to tackle economic inequality. The estate and gift tax, without an exemption for business property, is better suited to reduce inequality. If taxation should serve as a means against climate change, a global uniform tax on CO2 is necessary. Its level should correspond to the envisaged emissions reduction. Since environmental taxes cannot be avoided in the short and medium term, the resulting distribution effects have to be considered

Korngrößenanalysen an kalt- und warmfluvialen Sedimenten des Lechtales - Bayerisch -Schwaben

An grobklastischen Sedimenten des hoch-, spät- und postglazialen Lechtales wurden Korngrößenanalysen durchgeführt, die mittels Zerlegung ihrer multimodalen Häufigkeitsverteilungen in Einzelpopulationen ausgewertet und dargestellt werden. Auf diese Weise lassen sich die kalt-fluvialen Sedimente des Lechtales hinreichend gut von den holozänen warmfluvialen Ablagerungen differenzieren.researc

Molecular evolution and functional divergence of the bestrophin protein family

<p>Abstract</p> <p>Background</p> <p>Mutations in human bestrophin 1 are associated with at least three autosomal-dominant macular dystrophies including Best disease, adult onset vitelliform macular dystrophy and autosomal dominant vitreo-retinochoroidopathy. The protein is integral to the membrane and is likely involved in Ca²⁺-dependent transport of chloride ions across cellular membranes. Bestrophin 1 together with its three homologues forms a phylogenetically highly conserved family of proteins.</p> <p>Results</p> <p>A bioinformatics study was performed to investigate the phylogenetic relationship among the bestrophin family members and to statistically evaluate sequence conservation and functional divergence. Phylogenetic tree assembly with all available eukaryotic bestrophin sequences suggests gene duplication events in the lineage leading to the vertebrates. A common N-terminal topology which includes four highly conserved transmembrane domains is shared by the members of the four paralogous groups of vertebrate bestrophins and has been constrained by purifying selection. Pairwise comparison shows that altered functional constraints have occurred at specific amino acid positions after phylogenetic diversification of the paralogues. Most notably, significant functional divergence was found between bestrophin 4 and the other family members, as well as between bestrophin 2 and bestrophin 3. Site-specific profiles were established by posterior probability analysis revealing significantly divergent clusters mainly in two hydrophilic loops and a region immediately adjacent to the last predicted transmembrane domain. Strikingly, codons 279 and 347 of human bestrophin 4 reveal high divergence when compared to the paralogous positions strongly indicating the functional importance of these residues for the bestrophin 4 protein. None of the functionally divergent amino acids were found to reside within obvious sequences patterns or motifs.</p> <p>Conclusion</p> <p>Our study highlights the molecular evolution of the bestrophin family of transmembrane proteins and indicates amino acid residues likely relevant for distinct functional properties of the paralogues. These findings may provide a starting point for further experimental verifications.</p

Paneth Cell Secretion in vivo Requires Expression of Tmem16a and Tmem16f

Background and Aims Paneth cells play a central role in intestinal innate immune response. These cells are localized at the base of small intestinal crypts of Lieberkuhn. The calcium-activated chloride channel TMEM16A and the phospholipid scramblase TMEM16F control intracellular Ca2+ signaling and exocytosis. We analyzed the role of TMEM16A and TMEM16F for Paneth cells secretion. Methods Mice with intestinal epithelial knockout of Tmem16a (Tmem16a−/−) and Tmem16f (Tmem16f−/−) were generated. Tissue structures and Paneth cells were analyzed, and Paneth cell exocytosis was examined in small intestinal organoids in vitro. Intracellular Ca2+ signals were measured and were compared between wild-type and Tmem16 knockout mice. Bacterial colonization and intestinal apoptosis were analyzed. Results Paneth cells in the crypts of Lieberkuhn from Tmem16a−/− and Tmem16f−/− mice demonstrated accumulation of lysozyme. Tmem16a and Tmem16f were localized in wild-type Paneth cells but were absent in cells from knockout animals. Paneth cell number and size were enhanced in the crypt base and mucus accumulated in intestinal goblet cells of knockout animals. Granule fusion and exocytosis on cholinergic and purinergic stimulation were examined online. Both were strongly compromised in the absence of Tmem16a or Tmem16f and were also blocked by inhibition of Tmem16a/f. Purinergic Ca2+ signaling was largely inhibited in Tmem16a knockout mice. Jejunal bacterial content was enhanced in knockout mice, whereas cellular apoptosis was inhibited. Conclusion The present data demonstrate the role of Tmem16 for exocytosis in Paneth cells. Inhibition or activation of Tmem16a/f is likely to affect microbial content and immune functions present in the small intestine

Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract

Inflammatory airway diseases like cystic fibrosis, asthma and COVID-19 are characterized by high levels of pulmonary cytokines. Two well-established antiparasitic drugs, niclosamide and ivermectin, are intensively discussed for the treatment of viral inflammatory airway infections. Here, we examined these repurposed drugs with respect to their anti-inflammatory effects in airways in vivo and in vitro. Niclosamide reduced mucus content, eosinophilic infiltration and cell death in asthmatic mouse lungs in vivo and inhibited release of interleukins in the two differentiated airway epithelial cell lines CFBE and BCi-NS1.1 in vitro. Cytokine release was also inhibited by the knockdown of the Ca2+-activated Cl− channel anoctamin 1 (ANO1, TMEM16A) and the phospholipid scramblase anoctamin 6 (ANO6, TMEM16F), which have previously been shown to affect intracellular Ca2+ levels near the plasma membrane and to facilitate exocytosis. At concentrations around 200 nM, niclosamide inhibited inflammation, lowered intracellular Ca2+, acidified cytosolic pH and blocked activation of ANO1 and ANO6. It is suggested that niclosamide brings about its anti-inflammatory effects at least in part by inhibiting ANO1 and ANO6, and by lowering intracellular Ca2+ levels. In contrast to niclosamide, 1 µM ivermectin did not exert any of the effects described for niclosamide. The present data suggest niclosamide as an effective anti-inflammatory treatment in CF, asthma, and COVID-19, in addition to its previously reported antiviral effects. It has an advantageous concentration–response relationship and is known to be well tolerated