Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion

Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication

Towards time resolved core level photoelectron spectroscopy with femtosecond x-ray free-electron lasers

We have performed core level photoelectron spectroscopy on a W(110) single crystal with femtosecond XUV pulses from the free-electron laser at Hamburg (FLASH). We demonstrate experimentally and through theoretical modelling that for a suitable range of photon fluences per pulse, time-resolved photoemission experiments on solid surfaces are possible. Using FLASH pulses in combination with a synchronized optical laser, we have performed femtosecond time-resolved core-level photoelectron spectroscopy and observed sideband formation on the W 4f lines indicating a cross correlation between femtosecond optical and XUV pulses. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

Critical Susceptibility Exponent Measured from Fe/W(110) Bilayers

The critical phase transition in ferromagnetic ultrathin Fe/W(110) films has been studied using the magnetic ac susceptibility. A statistically objective, unconstrained fitting of the susceptibility is used to extract values for the critical exponent (gamma), the critical temperature Tc, the critical amplitude (chi_o) and the range of temperature that exhibits power-law behaviour. A fitting algorithm was used to simultaneously minimize the statistical variance of a power law fit to individual experimental measurements of chi(T). This avoids systematic errors and generates objective fitting results. An ensemble of 25 measurements on many different films are analyzed. Those which permit an extended fitting range in reduced temperature lower than approximately .00475 give an average value gamma=1.76+-0.01. Bilayer films give a weighted average value of gamma = 1.75+-0.02. These results are in agreement with the -dimensional Ising exponent gamma= 7/4. Measurements that do not exhibit power-law scaling as close to Tc (especially films of thickness 1.75ML) show a value of gamma higher than the Ising value. Several possibilities are considered to account for this behaviour.Comment: -Submitted to Phys. Rev. B -Revtex4 Format -6 postscript figure

Thresholding of the Elliott Yafet spin flip scattering in multi sublattice magnets by the respective exchange energies

How different microscopic mechanisms of ultrafast spin dynamics coexist and interplay is not only relevant for the development of spintronics but also for the thorough description of physical systems out of equilibrium. In pure crystalline ferromagnets, one of the main microscopic mechanism of spin relaxation is the electron phonon el ph driven spin flip, or Elliott Yafet, scattering. Unexpectedly, recent experiments with ferro and ferrimagnetic alloys have shown different dynamics for the different sublattices. These distinct sublattice dynamics are contradictory to the Elliott Yafet scenario. In order to rationalize this discrepancy, it has been proposed that the intra and intersublattice exchange interaction energies must be considered in the microscopic demagnetization mechanism, too. Here, using a temperature dependent x ray emission spectroscopy XES method, we address experimentally the element specific el ph angular momentum transfer rates, responsible for the spin flips in the respective sub lattices of Fe20Ni80, Fe50Ni50 and pure nickel single crystals. We establish how the deduced rate evolution with the temperature is linked to the exchange coupling constants reported for different alloy stoichiometries and how sublattice exchange energies threshold the related el ph spin flip channels. Thus, these results evidence that the Elliott Yafet spin flip scattering, thresholded by sublattice exchange energies, is the relevant microscopic process to describe sublattice dynamics in alloys and elemental magnetic system

Comparative study of an Eden model for the irreversible growth of spins and the equilibrium Ising model

The Magnetic Eden Model (MEM) with ferromagnetic interactions between nearest-neighbor spins is studied in $(d+1)-$dimensional rectangular geometries for $d = 1,2$. In the MEM, magnetic clusters are grown by adding spins at the boundaries of the clusters. The orientation of the added spins depends on both the energetic interaction with already deposited spins and the temperature, through a Boltzmann factor. A numerical Monte Carlo investigation of the MEM has been performed and the results of the simulations have been analyzed using finite-size scaling arguments. As in the case of the Ising model, the MEM in $d = 1$ is non-critical (only exhibits an ordered phase at $T= 0$). In $d = 2$ the MEM exhibits an order-disorder transition of second-order at a finite temperature. Such transition has been characterized in detail and the relevant critical exponents have been determined. These exponents are in agreement (within error bars) with those of the Ising model in 2 dimensions. Further similarities between both models have been found by evaluating the probability distribution of the order parameter, the magnetization and the susceptibility. Results obtained by means of extensive computer simulations allow us to put forward a conjecture which establishes a nontrivial correspondence between the MEM for the irreversible growth of spins and the equilibrium Ising model. This conjecture is certainly a theoretical challenge and its confirmation will contribute to the development of a framework for the study of irreversible growth processes.Comment: 21 pages, 11 figure

Study of general practitioner consultations for tick bites at high, medium and low incidence areas for Lyme borreliosis in England and Wales

Lyme borreliosis (LB) is a tick‐borne disease caused by Borrelia burgdorferi sensu lato complex. In Europe, it is predominately transmitted by the sheep tick, Ixodes ricinus. Compared with other European countries, the United Kingdom (UK) is considered to have a low incidence of LB, although this varies regionally. To determine whether an association exists between tick bite consultations and LB incidence in the UK, retrospective questionnaires were sent to general practitioners (GPs) in high (Wiltshire), medium (Cumbria) and low (Wales) incidence areas. During 2011, the greatest incidence of consultations for tick bites was reported by GPs in Cumbria (204 consultations per 100,000 inhabitants), followed by Wiltshire (160 per 100,000 population) and Wales (54 per 100,000 population). In Wiltshire and Cumbria, GPs predominantly provided advice on tick removal, whilst Welsh GPs mostly advised patients on tick bite prevention. Focusing on Cumbria during 2011–2013, 72.5% of GPs removed ticks from patients (incidence of 101 consultations per 100,000 population), and more GPs diagnosed LB based on clinical features than laboratory‐confirmed diagnoses. To date, this is the first study to investigate the incidence of tick bite consultations and LB in England and Wales

Magnetoresistance through a single molecule

The use of single molecules to design electronic devices is an extremely challenging and fundamentally different approach to further downsizing electronic circuits. Two-terminal molecular devices such as diodes were first predicted [1] and, more recently, measured experimentally [2]. The addition of a gate then enabled the study of molecular transistors [3-5]. In general terms, in order to increase data processing capabilities, one may not only consider the electron's charge but also its spin [6,7]. This concept has been pioneered in giant magnetoresistance (GMR) junctions that consist of thin metallic films [8,9]. Spin transport across molecules, i.e. Molecular Spintronics remains, however, a challenging endeavor. As an important first step in this field, we have performed an experimental and theoretical study on spin transport across a molecular GMR junction consisting of two ferromagnetic electrodes bridged by a single hydrogen phthalocyanine (H2Pc) molecule. We observe that even though H2Pc in itself is nonmagnetic, incorporating it into a molecular junction can enhance the magnetoresistance by one order of magnitude to 52%.Comment: To appear in Nature Nanotechnology. Present version is the first submission to Nature Nanotechnology, from May 18th, 201

The nature of frontier orbitals under systematic ligand exchange in pseudo octahedral Fe II complexes

Understanding and controlling properties of transition metal complexes is a crucial step towards tailoring materials for sustainable energy applications. In a systematic approach, we use resonant inelastic X ray scattering to study the influence of ligand substitution on the valence electronic structure around an aqueous iron II center. Exchanging cyanide with 2 20 bipyridine ligands reshapes frontier orbitals in a way that reduces metal 3d charge delocalization onto the ligands. This net decrease of metal ligand covalency results in lower metal centered excited state energies in agreement with previously reported excited state dynamics. Furthermore, traces of solvent effects were found indicating a varying interaction strength of the solvent with ligands of different character. Our results demonstrate how ligand exchange can be exploited to shape frontier orbitals of transition metal complexes in solution phase chemistry; insights upon which future efforts can built when tailoring the functionality of photoactive systems for light harvesting application

BigStitcher: reconstructing high-resolution image datasets of cleared and expanded samples.

Light-sheet imaging of cleared and expanded samples creates terabyte-sized datasets that consist of many unaligned three-dimensional image tiles, which must be reconstructed before analysis. We developed the BigStitcher software to address this challenge. BigStitcher enables interactive visualization, fast and precise alignment, spatially resolved quality estimation, real-time fusion and deconvolution of dual-illumination, multitile, multiview datasets. The software also compensates for optical effects, thereby improving accuracy and enabling subsequent biological analysis