491 research outputs found
Dynamics of allosteric transitions in GroEL
The chaperonin GroEL-GroES, a machine which helps some proteins to fold,
cycles through a number of allosteric states, the state, with high affinity
for substrate proteins (SPs), the ATP-bound state, and the
() complex. Structures are known for each
of these states. Here, we use a self-organized polymer (SOP) model for the
GroEL allosteric states and a general structure-based technique to simulate the
dynamics of allosteric transitions in two subunits of GroEL and the heptamer.
The transition, in which the apical domains undergo counter-clockwise
motion, is mediated by a multiple salt-bridge switch mechanism, in which a
series of salt-bridges break and form. The initial event in the transition, during which GroEL rotates clockwise, involves a
spectacular outside-in movement of helices K and L that results in K80-D359
salt-bridge formation. In both the transitions there is considerable
heterogeneity in the transition pathways. The transition state ensembles (TSEs)
connecting the , , and states are broad with the the
TSE for the transition being more plastic than the TSE. The results suggest that GroEL functions as a
force-transmitting device in which forces of about (5-30) pN may act on the SP
during the reaction cycle.Comment: 32 pages, 10 figures (Longer version than the one published
Rate equations for Coulomb blockade with ferromagnetic leads
We present a density-matrix rate-equation approach to sequential tunneling
through a metal particle weakly coupled to ferromagnetic leads. The
density-matrix description is able to deal with correlations between degenerate
many-electron states that the standard rate equation formalism in terms of
occupation probabilities cannot describe. Our formalism is valid for an
arbitrary number of electrons on the dot, for an arbitrary angle between the
polarization directions of the leads, and with or without spin-orbit scattering
on the metal particle. Interestingly, we find that the density-matrix
description may be necessary even for metal particles with unpolarized leads if
three or more single-electron levels contribute to the transport current and
electron-electron interactions in the metal particle are described by the
`universal interaction Hamiltonian'.Comment: 10 pages, 4 figures, REVTeX
Hard x ray spectroscopy and imaging by a reflection zone plate in the presence of astigmatism
The feasibility of an off axis x ray reflection zone plate to perform wavelength dispersive spectroscopy, on axis point focusing, and two dimensional imaging is demonstrated by means of one and the same diffractive optical element DOE at a synchrotron radiation facility. The resolving power varies between 30 and 400 in the range of 7.6 keV to 9.0 keV, with its maximum at the design energy of 8.3 keV. This result is verified using an adjustable entrance slit, by which horizontal H and vertical V focusing to 0.85 amp; 956;m H and 1.29 amp; 956;m V is obtained near the sagittal focal plane of the astigmatic configuration. An angular and axial scan proves an accessible field of view of at least 0.6 arcmin 0.8 arcmin and a focal depth of plus minus 0.86 mm. Supported by the grating efficiency of around 17.5 and a very short pulse elongation, future precision x ray fluorescence and absorption studies of transition metals at their K edge on an ultrashort timescale could benefit from our finding
Requirement of RIZ1 for cancer prevention by methyl-balanced diet
The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer
Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests
The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells.</p
Vibrational Excitations in Weakly Coupled Single-Molecule Junctions: A Computational Analysis
In bulk systems, molecules are routinely identified by their vibrational
spectrum using Raman or infrared spectroscopy. In recent years, vibrational
excitation lines have been observed in low-temperature conductance measurements
on single molecule junctions and they can provide a similar means of
identification. We present a method to efficiently calculate these excitation
lines in weakly coupled, gateable single-molecule junctions, using a
combination of ab initio density functional theory and rate equations. Our
method takes transitions from excited to excited vibrational state into account
by evaluating the Franck-Condon factors for an arbitrary number of vibrational
quanta, and is therefore able to predict qualitatively different behaviour from
calculations limited to transitions from ground state to excited vibrational
state. We find that the vibrational spectrum is sensitive to the molecular
contact geometry and the charge state, and that it is generally necessary to
take more than one vibrational quantum into account. Quantitative comparison to
previously reported measurements on pi-conjugated molecules reveals that our
method is able to characterize the vibrational excitations and can be used to
identify single molecules in a junction. The method is computationally feasible
on commodity hardware.Comment: 9 pages, 7 figure
Theory of Vibrationally Inelastic Electron Transport through Molecular Bridges
Vibrationally inelastic electron transport through a molecular bridge that is
connected to two leads is investigated. The study is based on a generic model
of vibrational excitation in resonant transmission of electrons through a
molecular junction. Employing methods from electron-molecule scattering theory,
the transmittance through the molecular bridge can be evaluated numerically
exactly. The current through the junction is obtained approximately using a
Landauer-type formula. Considering different parameter regimes, which include
both the case of a molecular bridge that is weakly coupled to the leads,
resulting in narrow resonance structures, and the opposite case of a broad
resonance caused by strong interaction with the leads, we investigate the
characteristic effects of coherent and dissipative vibrational motion on the
electron transport. Furthermore, the validity of widely used approximations
such as the wide-band approximation and the restriction to elastic transport
mechanisms is investigated in some detail.Comment: Submited to PRB, revised version according to comments of referees
(minor text changes and new citations
Erratum Polycapillary boosted instrument performance in the extreme ultraviolet regime for inverse photoemission spectroscopy erratum
We correct values and figures for the resolution of the spectrometer, as proposed in [Opt. Express 25, 31840 2017 ]. The new results take into account previously unknown, incoherent phase fluctuations, caused by the polycapillary lens PCL , and estimate the realistic performance of the instrumen
Polycapillary boosted instrument performance in the extreme ultraviolet regime for inverse photoemission spectroscopy
A collimating polycapillary half lens, traditionally used in the medium and hard X-ray band, is operated at a photon energy of 36 eV for the first time. While the transmission still exceeds 50%, the measured and simulated spatial resolution and angular divergence approach 0.4 mm or less and at most 20 mrad, respectively. This unexpected, superior performance of the polycapillary optic in the extreme Ultraviolet could enable the design of an e cient, versatile and compact spectrometer for inverse photoemission spectroscopy (IPES): Its wavelength-dispersive component, a customized reflection zone plate, can maintain an energy resolution of 0.3 eV, whereas the sensitivity may be enhanced by more than one order of magnitude, compared to conventional spectrometers. Furthermore, the overall length of 0.9 m would allow for an eased alignment and evacuation. We see a significant potential for numerous polycapillary-based XUV / soft X-ray instruments in the future, in particular after further optimization for this long wavelength regime
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