TY - INPR A1 - Dandekar, Thomas T1 - How do qubits interact? Implications for fundamental physics N2 - Proteins fold in water and achieve a clear structure despite a huge parameter space. Inside a (protein) crystal you have everywhere the same symmetries as there is everywhere the same unit cell. We apply this to qubit interactions to do fundamental physics: We modify cosmological inflation: we replace the big bang by a condensation event in an eternal all-encompassing ocean of free qubits. Rare interactions of qubits in the ocean provide a nucleus or seed for a new universe (domain), as the qubits become decoherent and freeze-out into defined bit ensembles. Next, we replace inflation by a crystallization event triggered by the nucleus of interacting qubits to which rapidly more and more qubits attach (like in everyday crystal growth). The crystal unit cell guarantees same symmetries (and laws of nature) everywhere inside the crystal, no inflation scenario is needed. Interacting qubits solidify, quantum entropy decreases in the crystal, but increases outside in the ocean. The interacting qubits form a rapidly growing domain where the n**m states become separated ensemble states, rising long-range forces stop ultimately further growth. After this very early modified steps, standard cosmology with the hot fireball model takes over. Our theory agrees well with lack of inflation traces in cosmic background measurements. Applying the Hurwitz theorem to qubits we prove that initiation of qubit interactions can only be 1,2,4 or 8-dimensional (agrees with E8 symmetry of our universe). Repulsive forces at ultrashort distances result from quantization, long-range forces limit crystal growth. The phase space of the crystal agrees with the standard model of the basic four forces for n quanta. It includes all possible ensemble combinations of their quantum states m, a total of n**m states. We describe a six-bit-ensemble toy model of qubit interaction and the repulsive forces of qubits for ultra-short distances. Neighbor states reach according to transition possibilities (S-matrix) with emergent time from entropic ensemble gradients. However, in our four dimensions there is only one bit overlap to neighbor states left (almost solid, only below Planck´s quantum is liquidity left). The E8 symmetry of heterotic string theory has six curled-up, small dimensions. These keep the qubit crystal together and never expand. We give energy estimates for free qubits vs bound qubits, misplacements in the qubit crystal and entropy increase during qubit crystal formation. Implications are fundamental answers, e.g. why there is fine-tuning for life-friendliness, why there is string theory with rolled-up dimension and so many free parameters. We explain by cosmological crystallization instead of inflation the early creation of large-scale structure of voids and filaments, supercluster formation, galaxy formation, and the dominance of matter: the unit cell of our crystal universe has a matter handedness avoiding anti-matter. Importantly, crystals come and go in the qubit ocean. This selects for the ability to lay seeds for new crystals, for self-organization and life-friendliness. Vacuum energy gets appropriate low inside the crystal by its qubit binding energy, outside it is 10**20 higher. Scalar fields for color interaction/confinement and gravity could be derived from the qubit-interaction field. KW - protein folding KW - qubit interaction KW - early cosmology KW - qubit KW - modified inflation KW - crystallization KW - decoherence Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357435 ER - TY - INPR A1 - Seitz, Florian A1 - Jungnickel, Tina A1 - Kleiber, Nicole A1 - Kretschmer, Jens A1 - Dietzsch, Julia A1 - Adelmann, Juliane A1 - Bohnsack, Katherine E. A1 - Bohnsack, Markus T. A1 - Höbartner, Claudia T1 - Atomic mutagenesis of N\(^6\)-methyladenosine reveals distinct recognition modes by human m\(^6\)A reader and eraser proteins T2 - Journal of the American Chemical Society N2 - N\(^6\)-methyladenosine (m\(^6\)A) is an important modified nucleoside in cellular RNA associated with multiple cellular processes and is implicated in diseases. The enzymes associated with the dynamic installation and removal of m\(^6\)A are heavily investigated targets for drug research, which requires detailed knowledge of the recognition modes of m\(^6\)A by proteins. Here, we use atomic mutagenesis of m\(^6\)A to systematically investigate the mechanisms of the two human m\(^6\)A demethylase enzymes FTO and ALKBH5 and the binding modes of YTH reader proteins YTHDF2/DC1/DC2. Atomic mutagenesis refers to atom-specific changes that are introduced by chemical synthesis, such as the replacement of nitrogen by carbon atoms. Synthetic RNA oligonucleotides containing site-specifically incorporated 1-deaza-, 3-deaza-, and 7-deaza-m\(^6\)A nucleosides were prepared by solid-phase synthesis and their RNA binding and demethylation by recombinant proteins were evaluated. We found distinct differences in substrate recognition and transformation and revealed structural preferences for the enzymatic activity. The deaza m\(^6\)A analogues introduced in this work will be useful probes for other proteins in m\(^6\)A research. KW - modified nucleosides KW - N6-methyladenosine (m6A) KW - atomic mutagenesis KW - YTH reader proteins KW - demethylase enzymes FTO and ALKBH5 Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-352376 ER - TY - INPR A1 - Dandekar, Thomas T1 - Protein folding and crystallization applied to qubit interactions and fundamental physics yields a modified inflation model for cosmology N2 - Protein folding achieves a clear solution structure in a huge parameter space (the so-called protein folding problem). Proteins fold in water, and get by this a highly ordered structure. Finally, inside a protein crystal for structure resolution, you have everywhere the same symmetries as there is everywhere the same unit cell. We apply this to qubit interactions to do fundamental physics: in a modified cosmology, we replace the big bang by a condensation event in an eternal all-encompassing ocean of free qubits. Interactions of qubits in the qubit ocean are quite rare but provide a nucleus or seed for a new universe (domain) as the qubits become decoherent and freeze-out into defined bit ensembles. Second, we replace inflation by a crystallization event triggered by the nucleus of interacting qubits to which rapidly more and more qubits attach (like in everyday crystal growth). The crystal unit cell guarantees same symmetries everywhere inside the crystal. The textbook inflation scenario to explain the same laws of nature in our domain is replaced by the unit cell of the crystal formed. Interacting qubits solidify, quantum entropy decreases (but increases in the ocean around). In a modified inflation scenario, the interacting qubits form a rapidly growing domain where the n**m states become separated ensemble states, rising long-range forces stop ultimately further growth. Then standard cosmology with the hot fireball model takes over. Our theory agrees well with lack of inflation traces in cosmic background measurements. We explain by cosmological crystallization instead of inflation: early creation of large-scale structure of voids and filaments, supercluster formation, galaxy formation, and the dominance of matter: the unit cell of our crystal universe has a matter handedness avoiding anti-matter. We prove initiation of qubit interactions can only be 1,2,4 or 8-dimensional (agrees with E8 symmetry of our universe). Repulsive forces at ultrashort distances result from quantization, long-range forces limit crystal growth. Crystals come and go in the qubit ocean. This selects for the ability to lay seeds for new crystals, for self-organization and life-friendliness. The phase space of the crystal agrees with the standard model of the basic four forces for n quanta. It includes all possible ensemble combinations of their quantum states m, a total of n**m states. Neighbor states reach according to transition possibilities (S-matrix) with emergent time from entropic ensemble gradients. However, in our four dimensions there is only one bit overlap to neighbor states left (almost solid, only below Planck quantum there is liquidity left). The E8 symmetry of heterotic string theory has six curled-up, small dimensions which help to keep the qubit crystal together and will never expand. Mathematics focusses on the Hurwitz proof applied to qubit interaction, a toy model of qubit interaction and repulsive forces of qubits. Vacuum energy gets appropriate low inside the crystal. We give first energy estimates for free qubits vs bound qubits, misplacements in the qubit crystal and entropy increase during qubit decoherence / crystal formation. Scalar fields for color interaction/confinement and gravity are derived from the qubit-interaction field. KW - protein folding KW - crystallization KW - qubit interaction KW - decoherence KW - modified inflation Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-346156 ER - TY - INPR A1 - Saal, Fridolin A1 - Swain, Asim A1 - Schmiedel, Alexander A1 - Holzapfel, Marco A1 - Lambert, Christoph A1 - Ravat, Prince T1 - Push-Pull [7]Helicene Diimide: Excited-State Charge Transfer and Solvatochromic Circularly Polarised Luminescence N2 - In this communication we describe a helically chiral push-pull molecule named 9,10-dimethoxy-[7]helicene diimide, displaying fluorescence (FL) and circularly polarised luminescence (CPL) over nearly the entire visible spectrum dependent on solvent polarity. The synthesised molecule exhibits an unusual solvent polarity dependence of FL quantum yield and nonradiative rate constant, as well as remarkable gabs and glum values along with high configurational stability. KW - Helicene diimide Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-345207 UR - https://doi.org/10.1039/D3CC04470J ET - submitted version ER - TY - INPR A1 - Warmdt, Julia A1 - Frisch, Henrik A1 - Ratz, Christoph A1 - Pohlmann-Rother, Sanna T1 - Digital lesen und erzählen. Eine Projektwoche für den inklusiven Anfangsunterricht T2 - Fördermagazin Grundschule N2 - Das Digital Storytelling bietet Schüler:innen im inklusiven Anfangsunterricht vielfältige Möglichkeiten der Teilhabe am Unterricht. Lesen Sie in diesem Beitrag, wie die Kinder eine digitale Geschichte auf unterschiedliche Art rezipieren und weitererzählen können. KW - Bilderbuch KW - Medienkompetenz KW - Inklusiver Unterricht KW - Anfangsunterricht KW - Erzählen KW - Digital Storytelling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328443 ET - accepted version ER - TY - INPR A1 - Neitz, Hermann A1 - Höbartner, Claudia T1 - A tolane-modified 5-ethynyluridine as a universal and fluorogenic photochemical DNA crosslinker T2 - Chemical Communications N2 - We report the fluorescent nucleoside ToldU and its application as a photoresponsive crosslinker in three different DNA architectures with enhanced fluorescence emission of the crosslinked products. The fluorogenic ToldU crosslinking reaction enables the assembly of DNA polymers in a hybridization chain reaction for the concentration-dependent detectio of a specific DNA sequence. KW - Tolane-Modified Fluorescent Nucleosides KW - Photoresponsive DNA Crosslinker Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328255 ET - submitted version ER - TY - INPR A1 - Dietzsch, Julia A1 - Jayachandran, Ajay A1 - Mueller, Stefan A1 - Höbartner, Claudia A1 - Brixner, Tobias T1 - Excitonic coupling of RNA-templated merocyanine dimer studied by higher-order transient absorption spectroscopy T2 - Chemical Communications N2 - We report the synthesis and spectroscopic analysis of RNA containing the barbituric acid merocyanine rBAM2 as a nucleobase surrogate. Incorporation into RNA strands by solid-phase synthesis leads to fluorescence enhancement compared to the free chromophore. In addition, linear absorption studies show the formation of an excitonically coupled H-type dimer in the hybridized duplex. Ultrafast third- and fifth-order transient absorption spectroscopy of this non-fluorescent dimer suggests immediate (sub-200 fs) exciton transfer and annihilation due to the proximity of the rBAM2 units. KW - Barbituric Acid Merocyanines KW - Nucleobase Surrogate Incorporation KW - Higher-order Transient Absorption Spectroscopy KW - rBAM2-labeled RNA strands Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-327772 ET - submitted version ER - TY - INPR A1 - Heidenreich, Julius F. A1 - Gassenmaier, Tobias A1 - Ankenbrand, Markus J. A1 - Bley, Thorsten A. A1 - Wech, Tobias T1 - Self-configuring nnU-net pipeline enables fully automatic infarct segmentation in late enhancement MRI after myocardial infarction N2 - Purpose To fully automatically derive quantitative parameters from late gadolinium enhancement (LGE) cardiac MR (CMR) in patients with myocardial infarction and to investigate if phase sensitive or magnitude reconstructions or a combination of both results in best segmentation accuracy. Methods In this retrospective single center study, a convolutional neural network with a U-Net architecture with a self-configuring framework (“nnU-net”) was trained for segmentation of left ventricular myocardium and infarct zone in LGE-CMR. A database of 170 examinations from 78 patients with history of myocardial infarction was assembled. Separate fitting of the model was performed, using phase sensitive inversion recovery, the magnitude reconstruction or both contrasts as input channels. Manual labelling served as ground truth. In a subset of 10 patients, the performance of the trained models was evaluated and quantitatively compared by determination of the Sørensen-Dice similarity coefficient (DSC) and volumes of the infarct zone compared with the manual ground truth using Pearson’s r correlation and Bland-Altman analysis. Results The model achieved high similarity coefficients for myocardium and scar tissue. No significant difference was observed between using PSIR, magnitude reconstruction or both contrasts as input (PSIR and MAG; mean DSC: 0.83 ± 0.03 for myocardium and 0.72 ± 0.08 for scars). A strong correlation for volumes of infarct zone was observed between manual and model-based approach (r = 0.96), with a significant underestimation of the volumes obtained from the neural network. Conclusion The self-configuring nnU-net achieves predictions with strong agreement compared to manual segmentation, proving the potential as a promising tool to provide fully automatic quantitative evaluation of LGE-CMR. KW - Deep learning KW - CMR KW - Segmentation KW - Myocardial infarction KW - Scar KW - nnU-net Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323418 UR - https://doi.org/10.1016/j.ejrad.2021.109817 ET - accepted version ER - TY - INPR A1 - Dandekar, Thomas T1 - A modified inflation cosmology relying on qubit-crystallization: rare qubit interactions trigger qubit ensemble growth and crystallization into “real” bit-ensembles and emergent time N2 - In a modified inflation scenario we replace the “big bang” by a condensation event in an eternal all-compassing big ocean of free qubits in our modified cosmology. Interactions of qubits in the qubit ocean are rare. If they happen, they provide a nucleus for a new universe as the qubits become decoherent and freeze-out into defined bit ensembles. Second, we replace inflation by a crystallization event triggered by the nucleus of interacting qubits to which rapidly more and more qubits attach (like in everyday crystal growth) – the crystal unit cell guarantees same symmetries everywhere. Hence, the textbook inflation scenario to explain the same laws of nature in our domain is replaced by the crystal unit cell of the crystal formed. We give here only the perspective or outline of this modified inflation theory, as the detailed mathematical physics behind this has still to be formulated and described. Interacting qubits solidify, quantum entropy decreases (but increases in the ocean around). The interacting qubits form a rapidly growing domain where the n**m states become separated ensemble states, rising long-range forces stop ultimately further growth. After that very early events, standard cosmology with the hot fireball model takes over. Our theory agrees well with lack of inflation traces in cosmic background measurements, but more importantly can explain well by such a type of cosmological crystallization instead of inflation the early creation of large-scale structure of voids and filaments, supercluster formation, galaxy formation, and the dominance of matter: no annihilation of antimatter necessary, rather the unit cell of our crystal universe has a matter handedness avoiding anti-matter. We prove a triggering of qubit interactions can only be 1,2,4 or 8-dimensional (agrees with E8 symmetry of our universe). Repulsive forces at ultrashort distances result from quantization, long-range forces limit crystal growth. Crystals come and go in the qubit ocean. This selects for the ability to lay seeds for new crystals, for self-organization and life-friendliness. The phase space of the crystal agrees with the standard model of the basic four forces for n quanta. It includes all possible ensemble combinations of their quantum states m, a total of n**m states. Neighbor states reach according to transition possibilities (S-matrix) with emergent time from entropic ensemble gradients. However, this means that in our four dimensions there is only one bit overlap to neighbor states left (almost solid, only below h dash liquidity left). However, the E8 symmetry of heterotic string theory has six rolled-up, small dimensions which help to keep the qubit crystal together and will never expand. Finally, we give first energy estimates for free qubits vs bound qubits, misplacements in the qubit crystal and entropy increase during qubit decoherence / crystal formation. Scalar fields for color interaction and gravity derive from the permeating qubit-interaction field in the crystal. Hence, vacuum energy gets low inside the qubit crystal. Condensed mathematics may advantageously help to model free (many states denote the same qubit) and bound qubits in phase space. KW - qubit KW - cosmology KW - decoherence KW - crystallization KW - emergent time Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321777 ER - TY - INPR A1 - Fersch, Daniel A1 - Malý, Pavel A1 - Rühe, Jessica A1 - Lisinetskii, Victor A1 - Hensen, Matthias A1 - Würthner, Frank A1 - Brixner, Tobias T1 - Single-Molecule Ultrafast Fluorescence-Detected Pump–Probe Microscopy N2 - We introduce fluorescence-detected pump–probe microscopy by combining a wavelength-tunable ultrafast laser with a confocal scanning fluorescence microscope, enabling access to the femtosecond time scale on the micrometer spatial scale. In addition, we obtain spectral information from Fourier transformation over excitation pulse-pair time delays. We demonstrate this new approach on a model system of a terrylene bisimide (TBI) dye embedded in a PMMA matrix and acquire the linear excitation spectrum as well as time-dependent pump–probe spectra simultaneously. We then push the technique towards single TBI molecules and analyze the statistical distribution of their excitation spectra. Furthermore, we demonstrate the ultrafast transient evolution of several individual molecules, highlighting their different behavior in contrast to the ensemble due to their individual local environment. By correlating the linear and nonlinear spectra, we assess the effect of the molecular environment on the excited-state energy. KW - Fluoreszenz KW - Ultrafast spectroscopy KW - Single-molecule microscopy Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313485 ER - TY - INPR A1 - Neitz, Hermann A1 - Bessi, Irene A1 - Kuper, Jochen A1 - Kisker, Caroline A1 - Höbartner, Claudia T1 - Programmable DNA interstrand crosslinking by alkene-alkyne [2+2] photocycloaddition T2 - Journal of the American Chemical Society N2 - Covalent crosslinking of DNA strands provides a useful tool for medical, biochemical and DNA nanotechnology applications. Here we present a light-induced interstrand DNA crosslinking reaction using the modified nucleoside 5-phenylethynyl-2’-deoxyuridine (\(^{Phe}\)dU). The crosslinking ability of \(^{Phe}\)dU was programmed by base pairing and by metal ion interaction at the Watson-Crick base pairing site. Rotation to intrahelical positions was favored by hydrophobic stacking and enabled an unexpected photochemical alkene-alkyne [2+2] cycloaddition within the DNA duplex, resulting in efficient formation of a \(^{Phe}\)dU-dimer after short irradiation times of a few seconds. A \(^{Phe}\)dU dimer-containing DNA was shown to efficiently bind a helicase complex, but the covalent crosslink completely prevented DNA unwinding, suggesting possible applications in biochemistry or structural biology. KW - light-induced interstrand DNA crosslinking KW - alkene-alkyne [2+2] photocycloaddition KW - DNA-based nanostructures KW - DNA-processing enzymes Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311822 N1 - This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Journal of the American Chemical Society, copyright © 2023 The Authors. Published by American Chemical Society. after peer review. To access the final edited and published work see https://doi.org/10.1021/jacs.3c01611. ET - submitted version ER - TY - INPR A1 - Dandekar, Thomas T1 - Analysing the phase space of the standard model and its basic four forces from a qubit phase transition perspective: implications for large-scale structure generation and early cosmological events N2 - The phase space for the standard model of the basic four forces for n quanta includes all possible ensemble combinations of their quantum states m, a total of n**m states. Neighbor states reach according to transition possibilities (S-matrix) with emergent time from entropic ensemble gradients. We replace the “big bang” by a condensation event (interacting qubits become decoherent) and inflation by a crystallization event – the crystal unit cell guarantees same symmetries everywhere. Interacting qubits solidify and form a rapidly growing domain where the n**m states become separated ensemble states, rising long-range forces stop ultimately further growth. After that very early events, standard cosmology with the hot fireball model takes over. Our theory agrees well with lack of inflation traces in cosmic background measurements, large-scale structure of voids and filaments, supercluster formation, galaxy formation, dominance of matter and life-friendliness. We prove qubit interactions to be 1,2,4 or 8 dimensional (agrees with E8 symmetry of our universe). Repulsive forces at ultrashort distances result from quantization, long-range forces limit crystal growth. Crystals come and go in the qubit ocean. This selects for the ability to lay seeds for new crystals, for self-organization and life-friendliness. We give energy estimates for free qubits vs bound qubits, misplacements in the qubit crystal and entropy increase during qubit decoherence / crystal formation. Scalar fields for color interaction and gravity derive from the permeating qubit-interaction field. Hence, vacuum energy gets low only inside the qubit crystal. Condensed mathematics may advantageously model free / bound qubits in phase space. KW - phase space KW - cosmology KW - emergent time KW - qubit KW - phase transition KW - bit Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-298580 ER - TY - INPR A1 - Scheitl, Carolin P. M. A1 - Mieczkowski, Mateusz A1 - Schindelin, Hermann A1 - Höbartner, Claudia T1 - Structure and mechanism of the methyltransferase ribozyme MTR1 T2 - Nature Chemical Biology N2 - RNA-catalysed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyses the site-specific synthesis of 1-methyladenosine (m\(^1\)A) in RNA, using O\(^6\)-methylguanine (m\(^6\)G) as methyl group donor. Here we report the crystal structure of MTR1 at a resolution of 2.8 Å, which reveals a guanine binding site reminiscent of natural guanine riboswitches. The structure represents the postcatalytic state of a split ribozyme in complex with the m1A-containing RNA product and the demethylated cofactor guanine. The structural data suggest the mechanistic involvement of a protonated cytidine in the methyl transfer reaction. A synergistic effect of two 2'-O-methylated ribose residues in the active site results in accelerated methyl group transfer. Supported by these results, it seems plausible that modified nucleotides may have enhanced early RNA catalysis and that metabolite-binding riboswitches may resemble inactivated ribozymes that have lost their catalytic activity during evolution. KW - Methyltransferase Ribozyme MTR1 KW - Crystal structure of MTR1 KW - RNA-catalyzed RNA methylation KW - X-ray crystallography KW - RNA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-272170 ET - submitted version ER - TY - INPR A1 - Hennig, Thomas A1 - Prusty, Archana B. A1 - Kaufer, Benedikt A1 - Whisnant, Adam W. A1 - Lodha, Manivel A1 - Enders, Antje A1 - Thomas, Julius A1 - Kasimir, Francesca A1 - Grothey, Arnhild A1 - Herb, Stefanie A1 - Jürges, Christopher A1 - Meister, Gunter A1 - Erhard, Florian A1 - Dölken, Lars A1 - Prusty, Bhupesh K. T1 - Selective inhibition of microRNA processing by a herpesvirus-encoded microRNA triggers virus reactivation from latency N2 - Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation thereof 1,2. A long appreciated, yet elusively defined relationship exists between the lytic-latent switch and viral non-coding RNAs 3,4. Here, we identify miRNA-mediated inhibition of miRNA processing as a novel cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defense and drive the latent-lytic switch. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective pri-miRNA hairpin loops. Subsequent loss of miR-30 and activation of miR-30/p53/Drp1 axis triggers a profound disruption of mitochondrial architecture, which impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 was sufficient to trigger virus reactivation from latency thereby identifying it as a readily drugable master regulator of the herpesvirus latent-lytic switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 provides exciting therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders like myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and Long-COVID. KW - Herpesvirus KW - HHV-6 KW - miRNA processing KW - miR-30 KW - mitochondria KW - fusion and fission KW - type I interferon KW - latency KW - virus reactivation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267858 UR - https://doi.org/10.21203/rs.3.rs-820696/v1 ET - submitted version ER - TY - INPR A1 - Dandekar, Thomas T1 - Qubit transition into defined Bits: A fresh perspective for cosmology and unifying theories N2 - In this view point we do not change cosmology after the hot fireball starts (hence agrees well with observation), but the changed start suggested and resulting later implications lead to an even better fit with current observations (voids, supercluster and galaxy formation; matter and no antimatter) than the standard model with big bang and inflation: In an eternal ocean of qubits, a cluster of qubits crystallizes to defined bits. The universe does not jump into existence (“big bang”) but rather you have an eternal ocean of qubits in free super-position of all their quantum states (of any dimension, force field and particle type) as permanent basis. The undefined, boiling vacuum is the real “outside”, once you leave our everyday universe. A set of n Qubits in the ocean are “liquid”, in very undefined state, they have all their m possibilities for quantum states in free superposition. However, under certain conditions the qubits interact, become defined, and freeze out, crystals form and give rise to a defined, real world with all possible time series and world lines. GR holds only within the crystal. In our universe all n**m quantum possibilities are nicely separated and crystallized out to defined bit states: A toy example with 6 qubits each having 2 states illustrates, this is completely sufficient to encode space using 3 bits for x,y and z, 1 bit for particle type and 2 bits for its state. Just by crystallization, space, particles and their properties emerge from the ocean of qubits, and following the arrow of entropy, time emerges, following an arrow of time and expansion from one corner of the toy universe to everywhere else. This perspective provides time as emergent feature considering entropy: crystallization of each world line leads to defined world lines over their whole existence, while entropy ensures direction of time and higher representation of high entropy states considering the whole crystal and all slices of world lines. The crystal perspective is also economic compared to the Everett-type multiverse, each qubit has its m quantum states and n qubits interacting forming a crystal and hence turning into defined bit states has only n**m states and not more states. There is no Everett-type world splitting with every decision but rather individual world trajectories reside in individual world layers of the crystal. Finally, bit-separated crystals come and go in the qubit ocean, selecting for the ability to lay seeds for new crystals. This self-organizing reproduction selects over generations also for life-friendliness. Mathematical treatment introduces quantum action theory as a framework for a general lattice field theory extending quantum chromo dynamics where scalar fields for color interaction and gravity have to be derived from the permeating qubit-interaction field. Vacuum energy should get appropriately low by the binding properties of the qubit crystal. Connections to loop quantum gravity, string theory and emergent gravity are discussed. Standard physics (quantum computing; crystallization, solid state physics) allow validation tests of this perspective and will extend current results. KW - qubit KW - cosmology KW - phase transition KW - unified theories KW - crystallization KW - emergent gravity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266418 ER - TY - INPR A1 - Sednev, Maksim V. A1 - Liaqat, Anam A1 - Höbartner, Claudia T1 - High-Throughput Activity Profiling of RNA-Cleaving DNA Catalysts by Deoxyribozyme Sequencing (DZ-seq) T2 - Journal of the American Chemical Society N2 - RNA-cleaving deoxyribozymes have found broad application as useful tools for RNA biochemistry. However, tedious in vitro selection procedures combined with laborious characterization of individual candidate catalysts hinder the discovery of novel catalytic motifs. Here, we present a new high-throughput sequencing method, DZ-seq, which directly measures activity and localizes cleavage sites of thousands of deoxyribozymes. DZ-seq exploits A-tailing followed by reverse transcription with an oligo-dT primer to capture the cleavage status and sequences of both deoxyribozyme and RNA substrate. We validated DZ-seq by conventional analytical methods and demonstrated its utility by discovery of novel deoxyribozymes that allow for cleaving challenging RNA targets or the analysis of RNA modification states. KW - RNA-Cleaving Deoxyribozymes KW - High-Throughput Sequencing Method, DZ-seq KW - Analysis of RNA Modifications Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258520 ER - TY - INPR A1 - Händel, Barbara A1 - Schölvinck, Marieke T1 - The brain during free movement – what can we learn from the animal model T2 - Brain Research N2 - Animals, just like humans, can freely move. They do so for various important reasons, such as finding food and escaping predators. Observing these behaviors can inform us about the underlying cognitive processes. In addition, while humans can convey complicated information easily through speaking, animals need to move their bodies to communicate. This has prompted many creative solutions by animal neuroscientists to enable studying the brain during movement. In this review, we first summarize how animal researchers record from the brain while an animal is moving, by describing the most common neural recording techniques in animals and how they were adapted to record during movement. We further discuss the challenge of controlling or monitoring sensory input during free movement. However, not only is free movement a necessity to reflect the outcome of certain internal cognitive processes in animals, it is also a fascinating field of research since certain crucial behavioral patterns can only be observed and studied during free movement. Therefore, in a second part of the review, we focus on some key findings in animal research that specifically address the interaction between free movement and brain activity. First, focusing on walking as a fundamental form of free movement, we discuss how important such intentional movements are for understanding processes as diverse as spatial navigation, active sensing, and complex motor planning. Second, we propose the idea of regarding free movement as the expression of a behavioral state. This view can help to understand the general influence of movement on brain function. Together, the technological advancements towards recording from the brain during movement, and the scientific questions asked about the brain engaged in movement, make animal research highly valuable to research into the human “moving brain”. KW - free movement KW - animal research KW - virtual reality KW - recording methods KW - brain activity Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251406 ET - accepted manuscript ER - TY - INPR A1 - Brych, Mareike A1 - Händel, Barbara T1 - Disentangling top-down and bottom-up influences on blinks in the visual and auditory domain T2 - International Journal of Psychophysiology N2 - Sensory input as well as cognitive factors can drive the modulation of blinking. Our aim was to dissociate sensory driven bottom-up from cognitive top-down influences on blinking behavior and compare these influences between the auditory and the visual domain. Using an oddball paradigm, we found a significant pre-stimulus decrease in blink probability for visual input compared to auditory input. Sensory input further led to an early post-stimulus blink increase in both modalities if a task demanded attention to the input. Only visual input caused a pronounced early increase without a task. In case of a target or the omission of a stimulus (as compared to standard input), an additional late increase in blink rate was found in the auditory and visual domain. This suggests that blink modulation must be based on the interpretation of the input, but does not need any sensory input at all to occur. Our results show a complex modulation of blinking based on top-down factors such as prediction and attention in addition to sensory-based influences. The magnitude of the modulation is mainly influenced by general attentional demands, while the latency of this modulation allows to dissociate general from specific top-down influences that are independent of the sensory domain. KW - eye blinks KW - attention KW - auditory KW - visual KW - visual domain KW - auditory domain KW - oddball Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246590 SN - 1872-7697 SN - 0167-8760 N1 - accepted version ER - TY - INPR A1 - Schaefer, Natascha A1 - Janzen, Dieter A1 - Bakirci, Ezgi A1 - Hrynevich, Andrei A1 - Dalton, Paul D. A1 - Villmann, Carmen T1 - 3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel T2 - Advanced Healthcare Materials N2 - 2D electrophysiology is often used to determine the electrical properties of neurons, while in the brain, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, we established 3D electrophysiology within a fiber-reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, we performed 3D electrophysiology on a glycine receptor-transfected Ltk-11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behaviour. The average thickness of the MEW scaffold was 141.4 ± 5.7µm, using 9.7 ± 0.2µm diameter fibers, and square pore spacings of 100 µm, 200 µm and 400 µm. We demonstrate, for the first time, the electrophysiological characterization of glycine receptor-transfected cells with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiology measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions. KW - 3D cultures Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244194 ER - TY - INPR A1 - Wolf, Norbert Richard T1 - Der Duden, die Genera und die Geschlechter T2 - Vestnik of Samara University. History, pedagogics, philology T2 - ВЕСТНИК САМАРСКОГО УНИВЕРСИТЕТА. ИСТОРИЯ, ПЕДАГОГИКА, ФИЛОЛОГИЯ N2 - Anlass für diesen Aufsatz ist die Tatsache, dass die Duden-Redaktion bei zahlreichen Personenbezeichnungen das sog. ‚generische Maskulinum‘ wegdefiniert hat. Das Anfang 2021 erschienene online Wörterbuch gibt als Bedeutungserklärung des Substantiv Arzt folgende Beschreibung an: „männliche Person, die nach Medizinstudium und klinischer Ausbildung die staatliche Zulassung (Approbation) erhalten hat, Kranke zu behandeln (Berufsbezeichnung)“. Demgegenüber hieß es im Duden Universalwörterbuch von 2015: „jemand, der nach Medizinstudium und klinischer Ausbildung die staatliche Zulassung (Approbation) erhalten hat, Kranke zu behandeln (Berufsbezeichnung)“ Der Aufsatz versucht, wieder einmal zu überprüfen, ob es das generische Maskulinum als geschlechtsübergreifende oder besser: geschlechtsneutrale Bezeichnung gibt oder ob es, nicht zuletzt aufgrund des jahrhundertelangen Einflusses des Patriarchats auf die Sprachentwicklung, sich doch um den Ausdruck männlicher Vormacht handelt. Dabei werden sowohl das Problem ‚Genus‘ als auch der Begriff ‚generisch‘ untersucht und auf seine Bezeichnungsfunktion hin getestet. Schließlich soll auch überprüft werden, ob die Sprache tatsächlich die Wirklichkeit widerspiegelt und ob die Sprache wirklich alle Phänomene in der außersprachlichen Realität benennen muss. Dazu kommt natürlich auch die Frage, ob die Duden-Redaktion ihre Kompetenzen richtig interpretiert (hat). KW - Duden KW - Genus KW - Sexus KW - lexikalische Bedeutung Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241571 UR - https://journals.ssau.ru/hpp/ ER -