224 research outputs found
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
Magnetic Scanning Tunneling Microscopy with a Two-Terminal Non-Magnetic Tip: Quantitative Results
We report numerical simulation result of a recently proposed \{P. Bruno,
Phys. Rev. Lett {\bf 79}, 4593, (1997)\} approach to perform magnetic scanning
tunneling microscopy with a two terminal non-magnetic tip. It is based upon the
spin asymmetry effect of the tunneling current between a ferromagnetic surface
and a two-terminal non-magnetic tip. The spin asymmetry effect is due to the
spin-orbit scattering in the tip. The effect can be viewed as a Mott scattering
of tunneling electrons within the tip. To obtain quantitative results we
perform numerical simulation within the single band tight binding model, using
recursive Green function method and Landauer-B\"uttiker formula for
conductance. A new model has been developed to take into account the spin-orbit
scattering off the impurities within the single-band tight-binding model. We
show that the spin-asymmetry effect is most prominent when the device is in
quasi-ballistic regime and the typical value of spin asymmetry is about 5%.Comment: 5 pages, Late
Recommended from our members
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
Non-adiabatic and time-resolved photoelectron spectroscopy for molecular systems
We quantify the non-adiabatic contributions to the vibronic sidebands of
equilibrium and explicitly time-resolved non-equilibrium photoelectron spectra
for a vibronic model system of Trans-Polyacetylene. Using exact
diagonalization, we directly evaluate the sum-over-states expressions for the
linear-response photocurrent. We show that spurious peaks appear in the
Born-Oppenheimer approximation for the vibronic spectral function, which are
not present in the exact spectral function of the system. The effect can be
traced back to the factorized nature of the Born-Oppenheimer initial and final
photoemission states and also persists when either only initial, or final
states are replaced by correlated vibronic states. Only when correlated initial
and final vibronic states are taken into account, the spurious spectral weights
of the Born-Oppenheimer approximation are suppressed. In the non-equilibrium
case, we illustrate for an initial Franck-Condon excitation and an explicit
pump-pulse excitation how the vibronic wavepacket motion of the system can be
traced in the time-resolved photoelectron spectra as function of the pump-probe
delay
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
Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice
A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens
Near edge x-ray absorption fine structure spectroscopy with x-ray free-electron lasers
Probing the Hofmeister Effect with Ultrafast Core Hole Spectroscopy
In the current work, X-ray emission spectra of aqueous solutions of different inorganic salts within the Hofmeister series are presented. The results reflect the direct interaction of the ions with the water molecules and therefore, reveal general properties of the salt-water interactions. Within the experimental precision a significant effect of the ions on the water structure has been observed but no ordering according to the structure maker/structure breaker concept could be mirrored in the results indicating that the Hofmeister effect-if existent-may be caused by more complex interactions
- …