Publikationen Natur- und Ingenieurwissenschaften 2018

Originalarbeiten in wissenschaftlichen Fachzeitschriften

Originalarbeiten in wissenschaftlichen Fachzeitschriften

Jahre: 2018

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2018

Pinnell R, de Vasconcelos A, Cassel J, Hofmann U
A Miniaturized, Programmable Deep-Brain Stimulator for Group-Housing and Water Maze Use
2018 FRONTIERS IN NEUROSCIENCE, Band: 12
KurzfassungPre-clinical deep-brain stimulation (DBS) research has observed a growing interest in the use of portable stimulation devices that can be carried by animals. Not only can such devices overcome many issues inherent with a cable tether, such as twisting or snagging, they can also be utilized in a greater variety of arenas, including enclosed or large mazes. However, these devices are not inherently designed for water-maze environments, and their use has been restricted to individually-housed rats in order to avoid damage from various social activities such as grooming, playing, or fighting. By taking advantage of 3D-printing techniques, this study demonstrates an ultra-small portable stimulator with an environmentally-protective device housing, that is suitable for both social-housing and water-maze environments. The miniature device offers 2 channels of charge-balanced biphasic pulses with a high compliance voltage (12 V), a magnetic switch, and a diverse range of programmable stimulus parameters and pulse modes. The device’s capabilities have been verified in both chronic pair-housing and water-maze experiments that asses the effects of nucleus reuniens DBS. Theta-burst stimulation delivered during a reference-memory water-maze task (but not before) had induced performance deficits during both the acquisition and probe trials of a reference memory task. The results highlight a successful application of 3D-printing for expanding on the range of measurement modalities capable in DBS research.
Rinschen M, ..., Kuettner V, Boerries M, Busch H, Dengjel J, Benzing T, Huber T
A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes
2018 CELL REPORTS, Band: 23, Nummer: 8, Seiten: 2495 - 2508
KurzfassungDamage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions. Integration of acquired omics dimensions suggested FARP1 as a candidate essential for podocyte function, which could be substantiated by genetic analysis in humans and knock-down experiments in zebrafish. This work exemplifies how the integration of multi-omics datasets can identify a framework of cell-type-specific features relevant for organ health and disease.
Sippel D, Rohde M, Netzer J, ..., Einsle O
A bound reaction intermediate sheds light on the mechanism of nitrogenase
2018 SCIENCE, Band: 359, Nummer: 6383
KurzfassungReduction of N-2 by nitrogenases occurs at an organometallic iron cofactor that commonly also contains either molybdenum or vanadium. The well-characterized resting state of the cofactor does not bind substrate, so its mode of action remains enigmatic. Carbon monoxide was recently found to replace a bridging sulfide, but the mechanistic relevance was unclear. Here we report the structural analysis of vanadium nitrogenase with a bound intermediate, interpreted as a mu(2)-bridging, protonated nitrogen that implies the site and mode of substrate binding to the cofactor. Binding results in a flip of amino acid glutamine 176, which hydrogen-bonds the ligand and creates a holding position for the displaced sulfide. The intermediate likely represents state E-6 or E-7 of the Thorneley-Lowe model and provides clues to the remainder of the catalytic cycle.
Johnson SR, McGown I, Oppermann U, Conwell LS, Harris M, Duncan EL
A novel INS mutation in a family with maturity-onset diabetes of the young: Variable insulin secretion and putative mechanisms
2018 Pediatr Diabetes, Band: 19, Seiten: 905 - 909
Niemann N, ..., Rothwell J, Leukel C
Assessing TMS-induced D and I waves with spinal H-reflexes
2018 JOURNAL OF NEUROPHYSIOLOGY, Band: 119, Nummer: 3, Seiten: 933 - 943
KurzfassungTranscranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters.
Kurz A, Lauber B, Franke S, Leukel C
Balance Training Reduces Postural Sway and Improves Sport-specific Performance in Visually Impaired Cross-Country Skiers.
2018 J Strength Cond Res
Hou S, ..., Hess W
Benefit from decline: the primary transcriptome of Alteromonas macleodii str. Te101 during Trichodesmium demise
2018 ISME JOURNAL, Band: 12, Nummer: 4, Seiten: 981 - 996
KurzfassungInteractions between co-existing microorganisms deeply affect the physiology of the involved organisms and, ultimately, the function of the ecosystem as a whole. Copiotrophic Alteromonas are marine gammaproteobacteria that thrive during the late stages of phytoplankton blooms in the marine environment and in laboratory co-cultures with cyanobacteria such as Trichodesmium. The response of this heterotroph to the sometimes rapid and transient changes in nutrient supply when the phototroph crashes is not well understood. Here, we isolated and sequenced the strain Alteromonas macleodii str. Te101 from a laboratory culture of Trichodesmium erythraeum IMS101, yielding a chromosome of 4.63 Mb and a single plasmid of 237 kb. Increasing salinities to >= 43 ppt inhibited the growth of Trichodesmium but stimulated growth of the associated Alteromonas. We characterized the transcriptomic responses of both microorganisms and identified the complement of active transcriptional start sites in Alteromonas at single-nucleotide resolution. In replicate cultures, a similar set of genes became activated in Alteromonas when growth rates of Trichodesmium declined and mortality was high. The parallel activation of fliA, rpoS and of flagellar assembly and growth-related genes indicated that Alteromonas might have increased cell motility, growth, and multiple biosynthetic activities. Genes with the highest expression in the data set were three small RNAs (Aln1a-c) that were identified as analogs of the small RNAs CsrB-C in E. coli or RsmX-Z in pathogenic bacteria. Together with the carbon storage protein A (CsrA) homolog Te101_05290, these RNAs likely control the expression of numerous genes in responding to changes in the environment.
Schuldt A, Assmann T, Brezzi M, Buscot F, Eichenberg D, Gutknecht J, Härdtle W, He JS, Klein AM, Kühn P, Liu X, Ma K, Niklaus PA, Pietsch KA, Purahong W, Scherer-Lorenzen M, Schmid B, Scholten T, Staab M, Tang Z, Trogisch S, von Oheimb G, Wirth C, Wubet T, Zhu CD, Bruelheide H
Biodiversity across trophic levels drives multifunctionality in highly diverse forests
2018 Nat Commun, Band: 9, Seite: 2989
Behler J, Vijay D, Hess WR, Akhtar MK
CRISPR-Based Technologies for Metabolic Engineering in Cyanobacteria.
2018 Trends Biotechnol
Hess WR, Hou S, Brenes-Alvarez M, Reimann V, Alkhnbashi OS, Backofen R, Muro-Pastor AM
CRISPR-Cas Systems in Multicellular Cyanobacteria.
2018 Rna Biol
Kieper S, ..., Hess W, Brouns S
Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation
2018 CELL REPORTS, Band: 22, Nummer: 13, Seiten: 3377 - 3384
KurzfassungCRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II CRISPR-Cas systems encode Cas4 proteins for which the role is unknown. Here, we introduced the CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system of Synechocystis sp. 6803 into Escherichia coli and observed that cas4 is strictly required for the selection of targets with protospacer adjacent motifs (PAMs) conferring I-D CRISPR interference in the native host Synechocystis. We propose a model in which Cas4 assists the CRISPR adaptation complex Cas1-2 by providing DNA substrates tailored for the correct PAM. Introducing functional spacers that target DNA sequences with the correct PAM is key to successful CRISPR interference, providing a better chance of surviving infection by mobile genetic elements.
Rode S, Bennett R, Buhmann S
Casimir effect for perfect electromagnetic conductors (PEMCs): a sum rule for attractive/repulsive forces
2018 NEW JOURNAL OF PHYSICS, Band: 20
KurzfassungWe discuss the Casimir effect for boundary conditions involving perfect electromagnetic conductors, which interpolate between perfect electric conductors and perfect magnetic conductors. Based on the corresponding reciprocal Green’s tensor we construct the Green’s tensor for two perfectly reflecting plates with magnetoelectric coupling (non-reciprocal media) within the framework of macroscopic quantum electrodynamics. We calculate the Casimir force between two arbitrary perfect electromagnetic conductor plates, resulting in a universal analytic expression that connects the attractive Casimir force with the repulsive Boyer force. We relate the results to a duality symmetry of electromagnetism.
Esfandiarpour S, Safari H, Bennett R, Buhmann S
Cavity-QED interactions of two correlated atoms
2018 JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS, Band: 51, Nummer: 9
KurzfassungWe consider the resonant van der Waals (vdW) interaction between two correlated identical two-level atoms (at least one of which being excited) within the framework of macroscopic cavity quantum electrodynamics in linear, dispersing and absorbing media. The interaction of both atoms with the body-assisted electromagnetic field of the cavity is assumed to be strong. Our time-independent evaluation is based on an extended Jaynes-Cummings model. For a system prepared in a superposition of its dressed states, we derive the general form of the vdW forces, using a Lorentzian single-mode approximation. We demonstrate the applicability of this approach by considering the case of a planar cavity and showing the position dependence of Rabi oscillations. We also show that in the limiting case of weak coupling, our results reproduce the perturbative ones for the case where the field is initially in vacuum state while the atomic state is in a superposition of two correlated states sharing one excitation.
Ditengou FA, Gomes D, Nziengui H, Kochersperger P, Lasok H, Medeiros V, Paponov IA, Nagy SK, Nadai TV, Meszaros T, Barnabas B, Ditengou BI, Rapp K, Qi L, Li X, Becker C, Li C, Doczi R, Palme K
Characterization of auxin transporter PIN6 plasma membrane targeting reveals a function for PIN6 in plant bolting.
2018 New Phytol, Band: 217, Nummer: 4, Seiten: 1610 - 1624
Schiedel M, Herp D, Hammelmann S, ..., Sippl W, Jung M
Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)
2018 JOURNAL OF MEDICINAL CHEMISTRY, Band: 61, Nummer: 2, SI, Seiten: 482 - 491
Berthold D, Breit B
Chemo-, Regio-, and Enantioselective Rhodium-Catalyzed Allylation of Triazoles with Internal Alkynes and Terminal Allenes
2018 ORGANIC LETTERS, Band: 20, Nummer: 3, Seiten: 598 - 601
KurzfassungThe rhodium-catalyzed asymmetric N-1-selective and regioselective coupling of triazole derivatives with internal alkynes and terminal allenes gives access to secondary and tertiary allylic triazoles in very good enantioselectivities. For this process, three new members of the JosPOphos ligand family have been prepared and employed in catalysis. The optimized reaction conditions enable the coupling of triazoles with internal alkynes as well as with allenes, displaying a high tolerance for functional groups. A gram scale reaction provided N-1-allyltriazole, which was subjected to various transformations highlighting synthetic utility.
Teikari J, Hou S, Wahlsten M, Hess W, Sivonen K
Comparative Genomics of the Baltic Sea Toxic Cyanobacteria Nodularia spumigena UHCC 0039 and Its Response to Varying Salinity
2018 FRONTIERS IN MICROBIOLOGY, Band: 9
KurzfassungSalinity is an important abiotic factor controlling the distribution and abundance of Nodularia spumigena, the dominating diazotrophic and toxic phototroph, in the brackish water cyanobacterial blooms of the Baltic Sea. To expand the available genomic information for brackish water cyanobacteria, we sequenced the isolate Nodularia spurn/germ UHCC 0039 using an Illumina-SMRT hybrid sequencing approach, revealing a chromosome of 5,294,286 base pairs (bp) and a single plasmid of 92,326 bp. Comparative genomics in Nostocales showed pronounced genetic similarity among Nodularia spumigena strains evidencing their short evolutionary history. The studied Baltic Sea strains share similar sets of CRISPR-Cas cassettes and a higher number of insertion sequence (IS) elements compared to Nodularia spumigena CENA596 isolated from a shrimp production pond in Brazil. Nodularia spumigena UHCC 0039 proliferated similarly at three tested salinities, whereas the lack of salt inhibited its growth and triggered transcriptome remodeling, including the up-regulation of five sigma factors and the down-regulation of two other sigma factors, one of which is specific for strain UHCC 0039. Down-regulated genes additionally included a large genetic region for the synthesis of two yet unidentified natural products. Our results indicate a remarkable plasticity of the Nodularia salinity acclimation, and thus salinity strongly impacts the intensity and distribution of cyanobacterial blooms in the Baltic Sea.
Shah SA, Alkhnbashi OS, Behler J, Han W, She Q, Hess WR, Garrett RA, Backofen R
Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-cas gene cassettes reveals 39 new cas gene families.
2018 Rna Biol, Seiten: 1 - 13
Lejeune J, ..., Gauthier C, Muellhaupt R
Creep and recovery analysis of polymeric materials during indentation tests
2018 EUROPEAN JOURNAL OF MECHANICS A-SOLIDS, Band: 68, Seiten: 1 - 8
KurzfassungThe present study describes comparative results obtained experimentally on two polymeric surfaces during contacts with a rigid spherical indenter. An experimental setup specifically dedicated to transparent materials has been used to analyze the creep phenomenon over long holding time segments (10(5) s) and to study the recovery process once contact has been removed. As a function of imposed contact time, a normalized value of representative strain is defined to quantify creep and recovery steps. Experimental results indicate that the recovery of the deformed surface after contact is mainly dependent on the initial contact time. Finite Elements Modeling will be used to discuss further the time-depending behaviors of the materials.
Middleton A, ..., Ronneberger O, Palme K, Fleck C, Dovzhenko A
Data-Driven Modeling of Intracellular Auxin Fluxes Indicates a Dominant Role of the ER in Controlling Nuclear Auxin Uptake
2018 CELL REPORTS, Band: 22, Nummer: 11, Seiten: 3044 - 3057
KurzfassungIn plants, the phytohormone auxin acts as a master regulator of developmental processes and environmental responses. The best characterized process in the auxin regulatory network occurs at the subcellular scale, wherein auxin mediates signal transduction into transcriptional programs by triggering the degradation of Aux/IAA transcriptional repressor proteins in the nucleus. However, whether and how auxin movement between the nucleus and the surrounding compartments is regulated remain elusive. Using a fluorescent auxin analog, we show that its diffusion into the nucleus is restricted. By combining mathematical modeling with time course assays on auxin-mediated nuclear signaling and quantitative phenotyping in single plant cell systems, we show that ER-to-nucleus auxin flux represents a major subcellular pathway to directly control nuclear auxin levels. Our findings propose that the homeostatically regulated auxin pool in the ER and ER-to-nucleus auxin fluxes underpin auxin-mediated downstream responses in plant cells.
Yang Y, Laird B
Droplet spreading on a surface exhibiting solid-liquid interfacial premelting
2018 ACTA MATERIALIA, Band: 143, Seiten: 319 - 328
KurzfassungWe study, using molecular-dynamics (MD) simulation, the spreading kinetics and equilibrium shape of liquid Pb droplets on an Al (111) substrate. The Al-Pb solid-liquid interface was found previously [Phys. Rev. Lett, 110, 096102 (2013)] to exhibit solid-liquid interfacial premelting at temperatures below the Al melting point. Because the Al(111) free surface does not exhibit premelting, the spreading of a Pb droplet is accompanied by a simultaneous surface transition from a faceted to a premelted Al substrate. Here, we examine how the coupling of the droplet spreading to the premelting affects the spreading kinetics and compare the results to two standard limiting mechanisms of droplet spreading: hydrodynamic spreading, in which the spreading energy dissipation is dominated by viscous relaxation, and kinetic spreading, where interfacial friction dominates. These two mechanisms predict different power-law dependency for the droplet radius versus time. For temperatures where premelting is present (between 875 K and the melting point of aluminum), kinetic spreading is observed at intermediate times. Because Pb droplets only partially wet the surface, the droplet radius at long times relaxes exponentially to the equilibrium droplet shape. Spreading simulations of a faceted system at 625 K [below the Al(111) roughening temperature] show that this system is consistent with a hydrodynamic spreading mechanism. However, when we examine a system at 922.38 K in which premelting is artificially suppressed by introducing harmonic constraints to give surface vibrations consistent with the AI(111) free surface, we observe a kinetic spreading mechanism-as in the premelted system. When premelting is suppressed, the equilibrium contact angle is observed to be significantly larger than when premelting is present even at the same temperatures. Thus, we conclude that the presence of the premelting layer has a significant effect on the thermodynamics Al(111)/Pb solid-liquid interface, but little effect on the mechanism of spreading. We also observe that the structure of the droplet contact line in the presence of the premelting layer is described by two contact angles (instead of the usual one) due to the presence of the additional pre melting layer, and resembles structures seen in reactive wetting systems. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Ganesan A
Epigenetic drug discovery: a success story for cofactor interference
2018 PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Band: 373, Nummer: 1748
KurzfassungWithin the past two decades, seven epigenetic drugs have received regulatory approval and numerous other candidates are currently in clinical trials. Among the epigenetic targets are the writer and eraser enzymes that are, respectively, responsible for the reversible introduction and removal of structural modifications in the nucleosome. This review discusses the progress achieved in the design and development of inhibitors against the key writer and eraser pairs: DNA methyltransferases and Tet demethylases; lysine/arginine methyltransferases and lysine demethylases; and histone acetyltransferases and histone deacetylases. A common theme for the successful inhibition of these enzymes in a potent and selective manner is the targeting of the cofactors present in the active site, namely zinc and iron cations, S-adenosylmethione, nicotinamide adenine dinucleotide, flavin adenine dinucleotide and acetyl Coenzyme A. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Ganesan A
Epigenetics: the first 25 centuries
2018 PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Band: 373, Nummer: 1748
KurzfassungEpigenetics is a natural progression of genetics as it aims to understand how genes and other heritable elements are regulated in eukaryotic organisms. The history of epigenetics is briefly reviewed, together with the key issues in the field today. This themed issue brings together a diverse collection of interdisciplinary reviews and research articles that showcase the tremendous recent advances in epigenetic chemical biology and translational research into epigenetic drug discovery. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Wiegel P, Niemann N, Rothwell J, Leukel C
Evidence for a subcortical contribution to intracortical facilitation
2018 EUROPEAN JOURNAL OF NEUROSCIENCE, Band: 47, Nummer: 11, Seiten: 1311 - 1319
KurzfassungIntracortical facilitation (ICF) describes the facilitation of an EMG response (motor evoked potential) to a suprathreshold pulse (S2) of transcranial magnetic stimulation (TMS) by a preceding subthreshold pulse (S1) given 10-15ms earlier. ICF is widely assumed to originate from intracortical mechanisms. In this study, we used spinal H-reflexes to test whether subcortical mechanisms can also contribute to the facilitation. Measurements were performed in the upper limb muscle flexor carpi radialis in 17 healthy volunteers, and in the lower limb muscle soleus in 16 healthy volunteers. S2 given alone facilitated the H-reflex. When S1 preceded S2 by 10ms, the amount of facilitation increased, compatible with ICF. However, S1 given alone also facilitated the H-reflex, suggesting that it had evoked descending activity even though its intensity was well below resting motor threshold. Across participants, the amount of H-reflex facilitation from S1 alone was proportional to the degree of H-reflex facilitation with combined S1-S2. These results indicate that subcortical mechanisms can contribute to ICF and potentially add to the variability of the ICF measure reported in previous studies.
Eckert A, Rudolph T, Guo J, Mang T, Walther A
Exceptionally Ductile and Tough Biomimetic Artificial Nacre with Gas Barrier Function.
2018 Adv Mater, Seiten: e1802477 - e1802477
Moser A, Hanssen H, Wandinger K-P
Excessively increased CSF glutamate levels in GABA(B)-receptor antibody associated encephalitis: A case report
2018 JOURNAL OF THE NEUROLOGICAL SCIENCES, Band: 388, Seiten: 10 - 11
Jiao D, Guo J, ..., Walther A
Facile and On-Demand Cross-Linking of Nacre-Mimetic Nanocomposites Using Tailor-Made Polymers with Latent Reactivity
2018 ACS APPLIED MATERIALS & INTERFACES, Band: 10, Nummer: 24, Seiten: 20250 - 20255
KurzfassungThe development of on-demand cross-linking strategies is a key aspect in promoting mechanical properties of high-performance bioinspired nanocomposites. Here, we embed styrene sulfonyl azide groups with latent chemical reactivity into water-soluble copolymers and assemble those with high-aspect-ratio synthetic nanoclays to generate well-defined layered polymer/nanoclay nacre-mimetics. A considerable stiffening and strengthening occurs upon activation of the covalent cross-linking using simple heating. Varying the amount of cross-linkable units allows molecular control of mechanical properties from ductile to stiff and strong. Moreover, the covalent cross-linking enhances the moisture stability of water-borne nacre-mimetics. The strategy is facile and versatile allowing for a transfer into applications.
Lott S, ..., Backofen R, Hess W, Voss B, Georg J
GLASSgo - Automated and Reliable Detection of sRNA Homologs From a Single Input Sequence
2018 FRONTIERS IN GENETICS, Band: 9
KurzfassungBacterial small RNAs (sRNAs) are important post-transcriptional regulators of gene expression. The functional and evolutionary characterization of sRNAs requires the identification of homologs, which is frequently challenging due to their heterogeneity, short length and partly, little sequence conservation. We developed the GLobal Automatic Small RNA Search go (GLASSgo) algorithm to identify sRNA homologs in complex genomic databases starting from a single sequence. GLASSgo combines an iterative BLAST strategy with pairwise identity filtering and a graph-based clustering method that utilizes RNA secondary structure information. We tested the specificity, sensitivity and runtime of GLASSgo, BLAST and the combination RNAlien/cmsearch in a typical use case scenario on 40 bacterial sRNA families. The sensitivity of the tested methods was similar, while the specificity of GLASSgo and RNAlien/cmsearch was significantly higher than that of BLAST. GLASSgo was on average similar to 87 times faster than RNAlien/cmsearch, and only similar to 7.5 times slower than BLAST, which shows that GLASSgo optimizes the trade-off between speed and accuracy in the task of finding sRNA homologs. GLASSgo is fully automated, whereas BLAST often recovers only parts of homologs and RNAlien/cmsearch requires extensive additional bioinformatic work to get a comprehensive set of homologs. GLASSgo is available as an easy-to-use web server to find homologous sRNAs in large databases.
Hagemann M, Gartner K, Scharnagl M, Bolay P, Lott SC, Fuss J, Huettel B, Reinhardt R, Klahn S, Hess WR
Identification of the DNA methyltransferases establishing the methylome of the cyanobacterium Synechocystis sp. PCC 6803.
2018 Dna Res
Quirynen R, Gros S, Diehl M
Inexact Newton-type optimization with iterated sensitivities
2018 SIAM JOURNAL ON OPTIMIZATION, Band: 28, Nummer: 1, Seiten: 74 - 95
Cribbs A, ..., Oppermann U
Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells
2018 JOURNAL OF BIOLOGICAL CHEMISTRY, Band: 293, Nummer: 7, Seiten: 2422 - 2437
KurzfassungNatural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets. The prototypic JMJD3/UTX (Jumonji domain-containing protein 3) H3K27 demethylase inhibitor GSK-J4 increased global levels of the repressive H3K27me3 mark around transcription start sites of effector cytokine genes. Moreover, GSK-J4 reduced IFN-gamma, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-10 levels in cytokine-stimulated NK cells while sparing their cytotoxic killing activity against cancer cells. The anti-inflammatory effect of GSK-J4 in NK cell subsets, isolated from peripheral blood or tissue from individuals with rheumatoid arthritis (RA), coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggested that histone demethylase inhibition has broad utility for modulating immune and inflammatory responses. Overall, our results indicate that H3K27me3 is a dynamic and important epigenetic modification during NK cell activation and that JMJD3/UTX-driven H3K27 demethylation is critical for NK cell function.
Grima R, ..., Fleck C
Insight into nuclear body formation of phytochromes through stochastic modelling and experiment
2018 PHYSICAL BIOLOGY, Band: 15, Nummer: 5
KurzfassungSpatial relocalization of proteins is crucial for the correct functioning of living cells. An interesting example of spatial ordering is the light-induced clustering of plant photoreceptor proteins. Upon irradiation by white or red light, the red light-active phytochrome, phytochrome B, enters the nucleus and accumulates in large nuclear bodies (NBs). The underlying physical process of nuclear body formation remains unclear, but phytochrome B is thought to coagulate via a simple protein-protein binding process. We measure, for the first time, the distribution of the number of phytochrome B-containing NBs as well as their volume distribution. We show that the experimental data cannot be explained by a stochastic model of nuclear body formation via simple protein-protein binding processes using physically meaningful parameter values. Rather modelling suggests that the data is consistent with a two step process: a fast nucleation step leading to macroparticles followed by a subsequent slow step in which the macroparticles bind to form the nuclear body. An alternative explanation for the observed nuclear body distribution is that the phytochromes bind to a so far unknown molecular structure. We believe it is likely this result holds more generally for other nu clear body-forming plant photoreceptors and proteins.
Chacoff NP, Resasco J, Vazquez DP
Interaction frequency, network position, and the temporal persistence of interactions in a plant-pollinator network.
2018 Ecology, Band: 99, Nummer: 1, Seiten: 21 - 28
Cao H, Klein AM, Zhu CD, Staab M, Durka W, Fischer M, Fornoff F
Intra- and interspecific tree diversity promotes multitrophic plant–Hemiptera–ant interactions in a forest diversity experiment
2018 Basic and Applied Ecology, Band: 29, Seiten: 89 - 97
Chillo V, Vazquez D, Amoroso M, Bennett E
Land-use intensity indirectly affects ecosystem services mainly through plant functional identity in a temperate forest
2018 FUNCTIONAL ECOLOGY, Band: 32, Nummer: 5, Seiten: 1390 - 1399
Kurzfassung1. Land-use change is known to affect biodiversity, and there is increasing concern regarding how these changes may impact the provision of ecosystem services. Although functional composition (diversity and identity) could influence ecosystem properties and services at the community level, there is little quantitative understanding of these relationships in the field. Here, we evaluate the direct and indirect effects (through ecosystem properties) of biodiversity on the provision of multiple ecosystem services in native mixed forest in north-west Patagonia, and how land-use intensity influences these relationships. 2. We used structural equation modelling to test hypotheses regarding the relationship between understorey plant functional composition, two ecosystem properties, four ecosystem services and silvopastoral use intensity (SUI). We also evaluated two alternative models to assess the mechanism behind biodiversity and ecosystem properties relationships (biomass ratio and niche complementarity). Finally, we performed pairwise correlations to identify synergies and tradeoffs between ecosystem services. 3. SUI affected functional composition, and the provision of three out of four ecosystem services was indirectly affected by land-use intensity through changes in ecosystem properties. We found that this indirect effect of biodiversity on ecosystem services happens mainly through changes in functional identity rather than functional diversity. Under increasing land-use intensity, functional composition changed towards a community characterized by a resource acquisition strategy. Trade-offs between ecosystem services (provisioning vs. regulating) were enhanced under high SUI, while synergies where enhanced under low SUI (provisioning vs. cultural). Thus, although the strength of these relationships varied-between SUI, its nature (trade-off or synergy) stayed the same. 4. Our results expand on previous studies by simultaneously considering the effect of land-use intensification directly on functional composition and on the ecosystem processes underpinning ecosystem services, as well as on the relationship among them. We provide evidence of an indirect effect of land-use intensification on multiple ecosystem services through biodiversity. Moreover, we found that functional identity is more important than diversity for ecosystem functionality. Land-use intensification affects biodiversity, and thus, ecosystem properties, but does not change the relationship among ecosystem services.
Weernink R, Barcellona P, Buhmann S
Lateral Casimir-Polder forces by breaking time-reversal symmetry
2018 PHYSICAL REVIEW A, Band: 97, Nummer: 3
KurzfassungWe examine the lateral Casimir-Polder force acting on a circular rotating emitter near a dielectric plane surface. As the circular motion breaks time-reversal symmetry, the spontaneous emission in a direction parallel to the surface is in general anisotropic. We show that a lateral force arises which can be interpreted as a recoil force because of this asymmetric emission. The force is an oscillating function of the distance between the emitter and the surface, and the lossy character of the dielectric strongly influences the results in the near-field regime. The force exhibits also a population-induced dynamics, decaying exponentially with respect to time on time scales of the inverse of the spontaneous decay rate. We propose that this effect could be detected measuring the velocity acquired by the emitter, following different cycles of excitation and spontaneous decay. Our results are expressed in terms of the Green’s tensor and can therefore easily be applied to more complex geometries.
Barcellona P, Bennett R, Buhmann S
Manipulating the Coulomb interaction: a Green’s function perspective
2018 JOURNAL OF PHYSICS COMMUNICATIONS, Band: 2, Nummer: 3
KurzfassungWe present a unified framework for studying Coulomb interactions in arbitrary environments using macroscopic quantum electrodynamics on the basis of the electromagnetic Green’s function. Our theory can be used to derive the Coulomb potential of a single charged particle as well as that between two charges in the presence of media, bodies and interfaces of arbitrary shapes. To demonstrate this, we reproduce the well-known screened Coulomb force, account for local-field effects and consider new cases such as a multi-layer medium, a dielectric cavity, a conducting wire and a plate with a hole.
Mramor B
Minimisers of the Allen-Cahn equation and the asymptotic Plateau problem on hyperbolic groups
2018 ANNALES DE L INSTITUT HENRI POINCARE-ANALYSE NON LINEAIRE, Band: 35, Nummer: 3, Seiten: 687 - 711
KurzfassungWe investigate the existence of non-constant uniformly-bounded minimal solutions of the Allen-Cahn equation on a Gromov-hyperbolic group. We show that whenever the Laplace term in the Allen-Cahn equation is small enough, there exist minimal solutions satisfying a large class of prescribed asymptotic behaviours. For a phase field model on a hyperbolic group, such solutions describe phase transitions that asymptotically converge towards prescribed phases, given by asymptotic directions. In the spirit of de Giorgi’s conjecture, we then fix an asymptotic behaviour and let the Laplace term go to zero. In the limit we obtain a solution to a corresponding asymptotic Plateau problem by F-convergence. (C) 2017 Elsevier Masson SAS. All rights reserved.
Drack J, Vazquez D
Morphological response of a cactus to cement dust pollution
2018 ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, Band: 148, Seiten: 571 - 577
KurzfassungCement dust from cement plants around the world has multiple negative effects on organisms and their environment. Cement’s effects come from its strongly alkaline nature and high content of heavy metals. Previous studies on plants have documented that cement dust deposition can influence plant vegetative growth, the lipid and ionic composition of tissues, and foliar temperature. Here we evaluate the effects of cement dust coming from a plant in westem Argentina on the morphology of the cactus Tephrocactus aoracanthus. In sites located at 0.15 km, 2 km and 6 km from the cement plant, we recorded five morphological attributes of the cactus: length and number of spines, cladode (stem) diameter, and fresh and dry weight. We also transplanted plants in situ to evaluate the effect of distance from the cement plant. In addition, we set an experiment spreading cement dust weekly on the aerial and ground parts of the cactus. Results of our field observational and experimental studies indicate that cement dust deposition on aerial parts of the plant leads to increased spine length, number of spines, and wet and dry weights of cladodes.
Teale W, Palme K
Naphthylphthalamic acid and the mechanism of polar auxin transport.
2018 J Exp Bot, Band: 69, Nummer: 2, Seiten: 303 - 312
Swyter S, ..., Sippl W, Jung M
New chemical tools for probing activity and inhibition of the NAD(+)-dependent lysine deacylase sirtuin 2
2018 PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Band: 373, Nummer: 1748
KurzfassungSirtuins are NAD(+)-dependent protein deacylases capable of cleaving off acetyl as well as other acyl groups from the e-amino group of lysines in histones and other substrate proteins. They have been reported as promising drug targets, and thus modulators of their activity are needed as molecular tools to uncover their biological function and as potential therapeutics. Here, we present new assay formats that complement existing assays for sirtuin biochemistry and cellular target engagement. Firstly, we report the development of a homogeneous fluorescence-based activity assay using unlabelled acylated peptides. Upon deacylation, the free lysine residue reacts with fluorescamine to form a fluotophore. Secondly, using click chemistry with a TAMRA-azide on a propargylated sirtuin inhibitor, we prepared the first fluorescently labelled small-molecule inhibitor of Sirt2. This is used in a binding assay, which is based on fluorescence polarization. We used it successfully to map potential inhibitor-binding sites and also to show cellular Sirt2 engagement. By means of these new assays, we were able to identify and characterize novel Sirt2 inhibitors out of a focused library screen. The binding of the identified Sirt2 inhibitors was rationalized by molecular docking studies. These new chemical tools thus can enhance further sirtuin research. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Fiedler J, Persson C, Bostrom M, Buhmann S
Orientational Dependence of the van der Waals Interactions for Finite-Sized Particles
2018 JOURNAL OF PHYSICAL CHEMISTRY A, Band: 122, Nummer: 19, Seiten: 4663 - 4669
KurzfassungDispersion forces, especially van der Waals forces as interactions between neutral and polarizable particles act at small distances between two objects. Their theoretical origin lies in the electromagnetic interaction between induced dipole moments caused by the vacuum fluctuations of the ground-state electromagnetic field. The resulting theory well describes the experimental situation in the limit of the point dipole assumption. At smaller distances, where the finite size of the particles has to be taken into account, this description fails and has to be corrected by higher orders of the multipole expansion, such as quadrupole moments and so on. With respect to the complexity of the spatial properties of the particles this task requires a considerable effort. In order to describe the van der Waals interaction between such particles, we apply the established method of a spatially spread out polarizability distribution to approximate the higher orders of the multipole expansion. We thereby construct an effective theory for effects from anisotropy and finite size on the van der Waals potential.
Zheng J, Breit B
Palladium-Catalyzed Direct C-H Allylation of Electron-Deficient Polyfluoroarenes with Alkynes
2018 ORGANIC LETTERS, Band: 20, Nummer: 7, Seiten: 1866 - 1870
KurzfassungA palladium-catalyzed intermolecular direct C-H allylation of polyfluoroarenes with alkynes is reported. Unlike classic hydroarylation reactions, alkynes are used as allylic electrophile surrogates in this direct aromatic C-H allylation. As an atom-economic and efficient method, various linear allylated fluoroarenes were synthesized from two simple and easy-to-access feedstocks in good to excellent yields, as well as regio- and stereoselectivity.
Merindol R, Loescher S, Samanta A, Walther A
Pathway-controlled formation of mesostructured all-DNA colloids and superstructures.
2018 Nat Nanotechnol
Hoenders D, Guo J, ..., Walther A
Photochemical ligation meets nanocellulose: a versatile platform for self-reporting functional materials
2018 MATERIALS HORIZONS, Band: 5, Nummer: 3, Seiten: 560 - 568
KurzfassungThe sustainable origin and highly promising mechanical and functional properties of cellulose nanofibrils (CNFs) attract significant interest for the construction of advanced functional materials. One key aspect of promoting the functionality of CNF-based materials is to implement sophisticated, facile and versatile chemical functionalization principles for application-targeted modification of CNF properties, independent of whether aiming for functional surfaces, hydrogels or bulk materials. We herein merge, for the first time, a self-reporting photo-induced modular ligation (the UV-induced nitrile imine-mediated tetrazole/ene cycloaddition, NITEC) with CNFs to control chemical functionality in space and time with the possibility for a macroscopic fluorescence readout of the reaction progress. We discuss this hetero-complementary photo-conjugation with respect to the immobilization of photoactive tetrazole units on CNFs in bulk and dispersion, and demonstrate the application for three important CNF-based material classes (surfaces, hydrogels and bioinspired nanocomposites) by modification with photo-complementary maleimide-tethered functional moieties. In addition to realizing selective biorecognition patterns on transparent nanopapers, we present photo-induced hydrogelation relevant for biomaterials, as well as mechanical stiffening in bioinspired nanocomposites in the bulk. The photochemical ligation proceeds smoothly in all three materials with vastly different dynamics (solution to bulk) and hence establishes a platform methodology to promote the self-reporting functionalization of diverse CNF-based materials.
Hu S, Musante L, Tataruch D, Xu X, Kretz O, Henry M, Meleady P, Luo H, Zou H, Jiang Y, Holthofer H
Purification and Identification of Membrane Proteins from Urinary Extracellular Vesicles using Triton X-114 Phase Partitioning.
2018 J Proteome Res, Band: 17, Nummer: 1, Seiten: 86 - 96
Zer H, Margulis K, Georg J, Shotland Y, Kostova G, Sultan LD, Hess WR, Keren N
Resequencing of a mutant bearing an iron starvation recovery phenotype defines Slr1658 as a new player in the regulatory network of a model cyanobacterium.
2018 Plant J, Band: 93, Nummer: 2, Seiten: 235 - 245
Ma Z, Huang Y, Park S, Kawai K, Kim DN, Hirai Y, Tsuchiya T, Yamada H, Tabata O
Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.
2018 Small, Band: 14, Nummer: 1
Bruenner T, Dufour G, Rodriguez A, Buchleitner A
Signatures of Indistinguishability in Bosonic Many-Body Dynamics
2018 PHYSICAL REVIEW LETTERS, Band: 120, Nummer: 21
KurzfassungThe dynamics of bosons in generic multimode systems, such as Bose-Hubbard models, arc not only determined by interactions among the particles, but also by their mutual indistinguishability manifested in many-particle interference. We introduce a measure of indistinguishability for Fock states of bosons whose mutual distinguishability is controlled by an internal degree of freedom. We demonstrate how this measure emerges both in the noninteracting and interacting evolution of observables. In particular, we find an unambiguous relationship between our measure and the variance of single-particle observables in the noninteracting limit. A nonvanishing interaction leads to a hierarchy of interaction-induced interference processes, such that even the expectation value of single-particle observables is influenced by the degree of indistinguishability.
Janssen A, Hunger H, Konold W, Pufal G, Staab M
Simple pond restoration measures increase dragonfly (Insecta: Odonata) diversity
2018 Biodivers Conserv, Band: 27, Seiten: 2311 - 2328
Repp S, ..., Weber S, Ocakoglu K, Erdem E
Synergetic effects of Fe3+ doped spinel Li4Ti5O12 nanoparticles on reduced graphene oxide for high surface electrode hybrid supercapacitors
2018 NANOSCALE, Band: 10, Nummer: 4, Seiten: 1877 - 1884
Grossman JJ, Vanhellemont M, Barsoum N, Bauhus J, Bruelheide H, Castagneyrol B, Cavender-Bares J, Eisenhauer N, Ferlian O, Gravel D, Hector A, Jactel H, Kreft H, Mereu S, Messier C, Muys B, Nock C, Paquette A, Parker J, Perring MP, Ponette Q, Reich PB, Schuldt A, Staab M, Weih M, Zemp DC, Scherer-Lorenzen M, Verheyen K
Synthesis and future research directions linking tree diversity to growth, survival, and damage in a global network of tree diversity experiments
2018 Environmental and Experimental Botany, Band: 152, Seiten: 68 - 89
Schwab MM, Himmel D, Kacprzak S, Radtke V, Kratzert D, Weis P, Wernet M, Peter A, Yassine Z, Schmitz D, Scheidt EW, Scherer W, Weber S, Feuerstein W, Breher F, Higelin A, Krossing I
Synthesis, Characterisation and Reactions of Truly Cationic Ni(I) -Phosphine Complexes.
2018 Chem-eur J, Band: 24, Nummer: 4, Seiten: 918 - 927
Staab M, Garcia FH, Liu C, Xu ZH, Economo EP
Systematics of the ant genus Proceratium Roger (Hymenoptera, Formicidae, Proceratiinae) in China - with descriptions of three new species based on micro-CT enhanced next-generation-morphology.
2018 Zookeys, Nummer: 770, Seiten: 137 - 192
Staab M, Hita Garcia F, Liu C, Xu ZH, Economo EP
Systematics of the ant genus Proceratium Roger (Hymenoptera, Formicidae, Proceratiinae) in China – with descriptions of three new species based on micro-CT enhanced next-generation-morphology
2018 Zookeys, Band: 770, Seiten: 137 - 192
Koegel J, ..., Himmel D, Krossing I, Sundermeyer J
The Lewis superacid Al[N(C6F5)(2)](3) and its higher homolog Ga[N(C6F5)(2)](3) - structural features, theoretical investigation and reactions of a metal amide with higher fluoride ion affinity than SbF5
2018 CHEMICAL SCIENCE, Band: 9, Nummer: 1, Seiten: 245 - 253
Behler J, ..., Wilde A, Urlaub H, Hess W
The host-encoded RNase E endonuclease as the crRNA maturation enzyme in a CRISPR-Cas subtype III-Bv system
2018 NATURE MICROBIOLOGY, Band: 3, Nummer: 3, Seiten: 367 - 377
KurzfassungSpecialized RNA endonucleases for the maturation of clustered regularly interspaced short palindromic repeat (CRISPR)derived RNAs (crRNAs) are critical in CRISPR-CRISPR-associated protein (Cas) defence mechanisms. The Cas6 and Cas5d enzymes are the RNA endonucleases in many class 1 CRISPR-Cas systems. In some class 2 systems, maturation and effector functions are combined within a single enzyme or maturation proceeds through the combined actions of RNase III and transactivating CRISPR RNAs (tracrRNAs). Three separate CRISPR-Cas systems exist in the cyanobacterium Synechocystis sp. PCC 6803. Whereas Cas6-type enzymes act in two of these systems, the third, which is classified as subtype III-B variant (III-Bv), lacks cas6 homologues. Instead, the maturation of crRNAs proceeds through the activity of endoribonuclease E, leaving unusual 13-and 14-nucleotide-long 5’-handles. Overexpression of RNase E leads to overaccumulation and knock-down to the reduced accumulation of crRNAs in vivo, suggesting that RNase E is the limiting factor for CRISPR complex formation. Recognition by RNase E depends on a stem-loop in the CRISPR repeat, whereas base substitutions at the cleavage site trigger the appearance of secondary products, consistent with a two-step recognition and cleavage mechanism. These results suggest the adaptation of an otherwise very conserved housekeeping enzyme to accommodate new substrates and illuminate the impressive plasticity of CRISPR-Cas systems that enables them to function in particular genomic environments.
Klein S, ..., Schiller S, Felthaus O, Dolderer J
Tissue engineering of adipose tissue with biodegradable biomaterials for soft tissue reconstruction
2018 HANDCHIRURGIE MIKROCHIRURGIE PLASTISCHE CHIRURGIE, Band: 50, Nummer: 2, Seiten: 83 - 92
KurzfassungSoft tissue defects resulting from injuries, tumor resection, congenital anomalies or chronic wounds pose a great challenge to reconstructive surgery. The current gold standard in therapy of such defects is the tissue transplantation in terms of free or local flaps. Unfortunately, donor site morbidity remains a considerable risk of flap surgery. Therefore, tissue engineering of autologous vascularized long term stable adipose tissue constructs could enrich the therapeutic possibilities of soft tissue defects. De novo adipose tissue growing requires fundamental knowledge about this kind of tissue and its synthesis, closely linked to angiogenesis. Bioresorbable biomaterials (scaffolds) are of crucial importance for adipose tissue engineering. Simulation or replacement of extracellular matrix for tissue growth by scaffold application requires a profound understanding of cell-matrix interactions. A proper biomaterial should be capable of supporting cell adherence, proliferation and differentiation. Important features are biocompatibility and resorption without toxic metabolites. In this review, various scaffold materials are discussed and novel achievements are presented. Persisting problems of de novo adipose tissue formation are high resorption rates and small tissue volumes of adipose constructs. Adipose tissue formation in a tissue engineering chamber is an additional possibility for in vivo tissue engineering. Recent studies proof that long term stable de novo adipose tissue formation of clinically relevant tissue volumes is possible. This method, in our opinion, has the potential to improve therapeutic strategies of soft tissue defects significantly.
Dittel C, Dufour G, ..., Buchleitner A, Keil R
Totally Destructive Many-Particle Interference
2018 PHYSICAL REVIEW LETTERS, Band: 120, Nummer: 24
KurzfassungIn a general, multimode scattering setup, we show how the permutation symmetry of a many-particle input state determines those scattering unitaries that exhibit strictly suppressed many-particle transition events. We formulate purely algebraic suppression laws that identify these events and show that the many particle interference at their origin is robust under weak disorder and imperfect indistinguishability of the interfering particles. Finally, we demonstrate that all suppression laws so far described in the literature are embedded in the general framework that we here introduce.
Müller M, Klein AM, Scherer-Lorenzen M, Nock C, Staab M
Tree genetic diversity increases arthropod diversity in willow short rotation coppice
2018 Biomass Bioenerg, Band: 108, Seiten: 338 - 344
Pitera M, Schmidt T
Unbiased estimation of risk
2018 J Bank Financ, Band: 91, Seiten: 133 - 145
Pitera M, Schmidt T
Unbiased estimation of risk
2018 JOURNAL OF BANKING & FINANCE, Band: 91, Seiten: 133 - 145
KurzfassungThe estimation of risk measures recently gained a lot of attention, partly because of the backtesting issues of expected shortfall related to elicitability. In this work we shed a new and fundamental light on optimal estimation procedures of risk measures in terms of bias. We show that once the parameters of a model need to be estimated, one has to take additional care when estimating risks. The typical plug-in approach, for example, introduces a bias which leads to a systematic underestimation of risk. In this regard, we introduce a novel notion of unbiasedness to the estimation of risk which is motivated by economic principles. In general, the proposed concept does not coincide with the well-known statistical notion of unbiasedness. We show that an appropriate bias correction is available for many well-known estimators. In particular, we consider value-at-risk and expected shortfall (tail value-at-risk). In the special case of normal distributions, closed-formed solutions for unbiased estimators can be obtained. We present a number of motivating examples which show the outperformance of unbiased estimators in many circumstances. The unbiasedness has a direct impact on backtesting and therefore adds a further viewpoint to established statistical properties. (C) 2018 Elsevier B.V. All rights reserved.
Giordano A, ..., Oppermann U, Di Micco S
Virtual Fragment Screening Identification of a Quinoline-5,8-dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor
2018 CHEMMEDCHEM, Band: 13, Nummer: 12, Seiten: 1160 - 1164
KurzfassungThe quinoline-5,8 dicarboxylic acid scaffold has been identified by a fragment-based approach as new potential lead compound for the development of JMJD3 inhibitors. Among them, 3-(2,4-dimethoxypyrimidin-5-yl)quinoline-5,8-dicarboxylic acid (compound 3) shows low micromolar inhibitory activity against Jumonji domain-containing protein3 (JMJD3). The experimental evaluation of inhibitory activity against seven related isoforms of JMJD3 highlighted an unprecedented selectivity toward the biological target of interest.
Joseph K, ..., Feuerstein T, Hofmann U
When the Ostrich-Algorithm Fails: Blanking Method Affects Spike Train Statistics
2018 FRONTIERS IN NEUROSCIENCE, Band: 12
KurzfassungModern electroceuticals are bound to employ the usage of electrical high frequency (130-180Hz) stimulation carried out under closed loop control, most prominent in the case of movement disorders. However, particular challenges are faced when electrical recordings of neuronal tissue are carried out during high frequency electrical stimulation, both in-vivo and in-vitro. This stimulation produces undesired artifacts and can render the recorded signal only partially useful. The extent of these artifacts is often reduced by temporarily grounding the recording input during stimulation pulses. In the following study, we quantify the effects of this method, “blanking,” on the spike count and spike train statistics. Starting from a theoretical standpoint, we calculate a loss in the absolute number of action potentials, depending on: width of the blanking window, frequency of stimulation, and intrinsic neuronal activity. These calculations were then corroborated by actual high signal to noise ratio (SNR) single cell recordings. We state that, for clinically relevant frequencies of 130Hz (used for movement disorders) and realistic blanking windows of 2 ms, up to 27% of actual existing spikes are lost. We strongly advice cautioned use of the blanking method when spike rate quantification is attempted. IMPACT STATEMENT Blanking (artifact removal by temporarily grounding input), depending on recording parameters, can lead to significant spike loss. Very careful use of blanking circuits is advised.
Burger F, Fiedler J, Buhmann S
Zero-point electromagnetic stress tensor for studying Casimir forces on colloidal particles in media
2018 EPL, Band: 121, Nummer: 2
KurzfassungWe address the question of the correct electromagnetic stress tensor in media and its consequences for the Casimir force. The latter being due to the zero-point momentum of the electromagnetic field, competing approaches based on the Abraham or Maxwell stress tensor lead to different predictions. We consider the test scenario of two colloidal spherical particles submerged in a dielectric medium and use three criteria to distinguish the two approaches: we show that the Abraham stress tensor, and not the Maxwell stress tensor, leads to a Casimir force that is form-equivalent to Casimir-Polder and van der Waals forces, obeys duality as a fundamental symmetry and is consistent with microscopic many-body calculations. On this basis, we derive general formulas for the dispersion forces on one and between two colloidal particles in arbitrary liquid-media environments in terms of their dipole polarisabilities, allowing for more elaborate theoretical descriptions and bridging the gap between microscopic and macroscopic accounts. Copyright (C) EPLA, 2018