Chronology of Lake El'gygytgyn sediments – a combined magnetostratigraphic, palaeoclimatic and orbital tuning study based on multi-parameter analyses

A 318-metre-long sedimentary profile drilled by the International Continental Scientific Drilling Program (ICDP) at Site 5011-1 in Lake El’gygytgyn, Far East Russian Arctic, has been analysed for its sedimentologic response to global climate modes by chronostratigraphic methods. The 12 km wide lake is sited off-centre in an 18 km large crater that was created by the impact of a meteorite 3.58 Ma ago. Since then sediments have been continuously deposited. For establishing their chronology, major reversals of the earth’s magnetic field provided initial tie points for the age model, confirming that the impact occurred in the earliest geomagnetic Gauss chron. Various stratigraphic parameters, reflecting redox conditions at the lake floor and climatic conditions in the catchment were tuned synchronously to Northern Hemisphere insolation variations and the marine oxygen isotope stack, respectively. Thus, a robust age model comprising more than 600 tie points could be defined. It could be shown that deposition of sediments in Lake El’gygytgyn occurred in concert with global climatic cycles. The upper �160m of sediments represent the past 3.3 Ma, equivalent to sedimentation rates of 4 to 5 cm ka−1, whereas the lower 160m represent just the first 0.3 Ma after the impact, equivalent to sedimentation rates in the order of 45 cm ka−1. This study also provides orbitally tuned ages for a total of 8 tephras deposited in Lake El’gygytgyn.

Electronic tuning effects via cyano substitution of a fused tetrathiafulvalene–benzothiadiazole dyad for ambipolar transport properties

Electronic tuning effects of substituents at the 4- and 8-positions of benzothiadiazole (BTD) within the fused tetrathiafulvalene–BTD donor–acceptor dyad have been studied. The electron acceptor strength of BTD is greatly increased by replacing Br with CN groups, extending the optical absorption of the small dyad into the near-IR region and importantly, the charge transport can be switched from p-type to ambipolar behaviour.

Tuning curve of type-0 spontaneous parametric down-conversion

We study the tuning curve of entangled photons generated by type-0 spontaneous parametric down-conversion in a periodically poled potassium titanyl phosphate crystal. We demonstrate the X-shaped spatiotemporal structure of the spectrum by means of measurements and numerical simulations. Experiments for different pump waists, crystal temperatures, and crystal lengths are in good agreement with numerical simulations.

Personalized Tuning of a Reinforcement Learning Control Algorithm for Glucose Regulation

Artificial pancreas is in the forefront of research towards the automatic insulin infusion for patients with type 1 diabetes. Due to the high inter- and intra-variability of the diabetic population, the need for personalized approaches has been raised. This study presents an adaptive, patient-specific control strategy for glucose regulation based on reinforcement learning and more specifically on the Actor-Critic (AC) learning approach. The control algorithm provides daily updates of the basal rate and insulin-to-carbohydrate (IC) ratio in order to optimize glucose regulation. A method for the automatic and personalized initialization of the control algorithm is designed based on the estimation of the transfer entropy (TE) between insulin and glucose signals. The algorithm has been evaluated in silico in adults, adolescents and children for 10 days. Three scenarios of initialization to i) zero values, ii) random values and iii) TE-based values have been comparatively assessed. The results have shown that when the TE-based initialization is used, the algorithm achieves faster learning with 98%, 90% and 73% in the A+B zones of the Control Variability Grid Analysis for adults, adolescents and children respectively after five days compared to 95%, 78%, 41% for random initialization and 93%, 88%, 41% for zero initial values. Furthermore, in the case of children, the daily Low Blood Glucose Index reduces much faster when the TE-based tuning is applied. The results imply that automatic and personalized tuning based on TE reduces the learning period and improves the overall performance of the AC algorithm.

Tuning Molecular Recognition of RNA and DNA via Sugar Modification

This minireview highlights three aspects of our recent work in the area of sugar modified oligonucleotide analogues. It provides an overview over recent results on the conformationally constrained analogue tricyclo-DNA with special emphasis of its antisense properties, it summarizes results on triple-helix forming oligodeoxynucleotides containing pyrrolidino-nucleosides with respect to DNA recognition via the dual recognition mode, and it highlights the advantageous application of the orthogonal oligonucleotidic pairing system homo-DNA in molecular beacons for DNA diagnostics

When small non-coding RNAs meet the ribosome: Tuning the translational machinery

The functions of ribosomes in translation are complex and involve different types of activities critical for decoding the genetic code, linkage of amino acids via amide bonds to form polypeptide chains, as well as the release and proper targeting of the synthesized protein. Non-protein-coding RNAs (ncRNAs) have been recognized to be crucial in establishing regulatory networks.1 However all of the recently discovered ncRNAs involved in translation regulation target the mRNA rather than the ribosome. The main goal of this project is to identify potential novel ncRNAs that directly bind and possibly regulate the ribosome during protein biosynthesis. To address this question we applied various stress conditions to the archaeal model organism Haloferax volcanii and deep-sequenced the ribosome-associated small ncRNA interactome. In total we identified 6.250 ncRNA candidates. Significantly, we observed the emersed presence of tRNA-derived fragments (tRFs). These tRFs have been identified in all domains of life and represent a growing, yet functionally poorly understood, class of ncRNAs. Here we present evidence that tRFs from H. volcanii directly bind to ribosomes. In the presented genomic screen of the ribosome-associated RNome a 26 residue long fragment originating from the 5’ part of valine tRNA was by far the most abundant tRF. The Val-tRF is processed in a stress- dependent manner and was found to primarily target the small ribosomal subunit in vitro and in vivo. As a consequence of ribosome binding, Val-tRF reduces protein synthesis by interfering with peptidyl transferase activity. Therefore this tRF functions as ribosome-bound small ncRNA capable of regulating gene expression in H. volcanii under environmental stress conditions probably by fine-tuning the rate of protein production.2 Currently we are investigating the binding site of this tRF on the 30S subunit in more detail.

Tuning the in vitro cell cytotoxicity of dinuclear arene ruthenium trithiolato complexes: Influence of the arene ligand

A new series of cationic dinuclear arene ruthenium complexes bridged by three thiophenolato ligands, [(η6-arene)2Ru2(μ2-SR)3]+ with arene = indane, R = met: 1 (met = 4-methylphenyl); R = mco: 4 (mco = 4-methylcoumarin-7-yl); arene = biphenyl, R = met: 2; R = mco: 5; arene = 1,2,3,4-tetrahydronaphthalene, R = met: 3; R = mco: 6, have been prepared from the reaction of the neutral precursor [(η6-arene)Ru(μ2-Cl)Cl]2 and the corresponding thiophenol RSH. All cationic complexes have been isolated as chloride salts and fully characterized by spectroscopic and analytical methods. The molecular structure of 1, solved by X-ray structure analysis of a single crystal of the chloride salt, shows the two ruthenium atoms adopting a pseudo-octahedral geometry without metal–metal bond in accordance with the noble gas rule. All complexes are stable in H2O at 37 °C, but only 1 remains soluble in a 100 mM aqueous NaCl solution, while significant percentages (30–60 %) of 2–6 precipitate as chloride salts under these conditions. The 4-methylphenylthiolato complexes (R = met) are highly cytotoxic towards human ovarian cancer cells, the IC50 values being in the sub-micromolar range, while the 4-methylcoumarin-7-yl thiolato complexes (R = mco) are only slightly cytotoxic. Complexes 1 and 3 show the highest in vitro anticancer activity with IC50 values inferior to 0.06 μM for the A2780 cell line. The results demonstrate that the arene ligand is an important parameter that should be more systematically evaluated when designing new half-sandwich organometallic complexes.

Electronic tuning effects via π-linkers in tetrathiafulvalene-based dyes

Four new tetrathiafulvalene (TTF)-based dyes featured with a donor–bridge–acceptor (D–π–A) structure were synthesized and characterized. All of them undergo two reversible oxidations to form stable radical cation and dication species. The electronic interactions between the TTF donor and the cyanoacrylic acid acceptor through the different π-linkers have been demonstrated by the presence of a photo-induced intramolecular charge-transfer (ICT) absorption band in the visible region. A red shift of the ICT state can be finely tuned by the degree of aromaticity and extended conjugation of π-bridges. To some extent, the oxidation potentials of these dyes are affected by the nature of π-bridges. They have been applied in organic dye-sensitized solar cells, showing relatively low power conversion efficiencies of up to 0.87% due to substantial charge recombination losses.

Microbiota-mediated fine-tuning of the threshold of intestinal inflammasome activation in host-microbial mutualism

The inflammasome is a complex of proteins that controls the activity of caspase-1, pro-IL-1b and pro-IL-18. It acts in inflammatory processes and in pyropoptosis. The lower intestine is densely populated by a community of commensal bacteria that, under healthy conditions, are beneficial to the host. Some evidence suggests that the gut microbiota influences regulation of the inflammasome. Components of inflammasomes have been shown to have a protective function against development of experimental colitis, dependent on IL-18 production. However the precise mechanisms and the role of the inflammasome in maintaining a healthy host-microbial mutualism remains unknown. To address this question, we have performed axenic (GF) and gnotobiotic in vivo experiments to investigate how the inflammasome components mainly at the level of intestinal epithelial cells (IECs) are regulated under different hygiene conditions. We have established that gene expression of the inflammasome components NLRC4, NLRP3, NLRP6, NLRP12, caspase-1, ASC and IL-18 do not differ between germ-free and colonised conditions under steady-state. In contrast, induction in IL-18 was observed following infection with the pathobiont Segmented Filamentous Bacteria or the pathogen C. rodentium. Additional preliminar findings suggest that a more diverse intestinal flora, like specific pathogen-free (SPF) flora, is more efficient in inducing basal activation of the inflammasome and especially production of IL-18 by IECs, shortly after colonisation. We are also in the process of testing if basal activation of the inflammasome upon intestinal colonization with commensal bacteria helps to protect the host from potential pathobiont bacteria, like C. rodentium, SFB, Prevotella and TM7.

Photopic and scotopic spatiotemporal tuning of adult zebrafish vision.

Sensitivity to spatial and temporal patterns is a fundamental aspect of vision. Herein, we investigated this sensitivity in adult zebrafish for a wide range of spatial (0.014 to 0.511 cycles/degree [c/d]) and temporal frequencies (0.025 to 6 cycles/s) to better understand their visual system. Measurements were performed at photopic (1.8 log cd m(-2)) and scotopic (-4.5 log cd m(-2)) light levels to assess the optokinetic response (OKR). The resulting spatiotemporal contrast sensitivity (CS) functions revealed that the OKR of zebrafish is tuned to spatial frequency and speed but not to temporal frequencies. Thereby, optimal test parameters for CS measurements were identified. At photopic light levels, a spatial frequency of 0.116 ± 0.01 c/d (mean ± SD) and a grating speed of 8.42 ± 2.15 degrees/second (d/s) was ideal; at scotopic light levels, these values were 0.110 ± 0.02 c/d and 5.45 ± 1.31 d/s, respectively. This study allows to better characterize zebrafish mutants with altered vision and to distinguish between defects of rod and cone photoreceptors as measurements were performed under different light conditions.