64 research outputs found

    Does backreaction enforce the averaged null energy condition in semiclassical gravity?

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    The expected stress-energy tensor of quantum fields generically violates the local positive energy conditions of general relativity. However, may satisfy some nonlocal conditions such as the averaged null energy condition (ANEC), which would rule out traversable wormholes. Although ANEC holds in Minkowski spacetime, it can be violated in curved spacetimes if one is allowed to choose the spacetime and quantum state arbitrarily, without imposition of the semiclassical Einstein equation G_{ab} = 8 \pi . In this paper we investigate whether ANEC holds for solutions to this equation, by studying a free, massless scalar field with arbitrary curvature coupling in perturbation theory to second order about the flat spacetime/vacuum solution. We "reduce the order" of the perturbation equations to eliminate spurious solutions, and consider the limit in which the lengthscales determined by the incoming state are much larger than the Planck length. We also need to assume that incoming classical gravitational radiation does not dominate the first order metric perturbation. We find that although the ANEC integral can be negative, if we average the ANEC integral transverse to the geodesic with a suitable Planck scale smearing function, then a strictly positive result is obtained in all cases except for the flat spacetime/vacuum solution. This result suggests --- in agreement with conclusions drawn by Ford and Roman from entirely independent arguments --- that if traversable wormholes do exist as solutions to the semiclassical equations, they cannot be macroscopic but must be ``Planck scale''. A large portion of our paper is devoted to the analysis of general issues concerning the nature of the semiclassical Einstein equation and of prescriptions for extracting physically relevant solutions.Comment: 54 pages, 3 figures, uses revtex macros and epsf.tex, to appear in Phys Rev D. A new appendix has been added showing consistency of our results with recent results of Visser [gr-qc/9604008]. Some corrections were made to Appendix A, and several other minor changes to the body of the paper also were mad

    Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation

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    Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APCMin/+ mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy

    Energy and directional signatures for plane quantized gravity waves

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    Solutions are constructed to the quantum constraints for planar gravity (fields dependent on z and t only) in the Ashtekar complex connection formalism. A number of operators are constructed and applied to the solutions. These include the familiar ADM energy and area operators, as well as new operators sensitive to directionality (z+ct vs. z-ct dependence). The directionality operators are quantum analogs of the classical constraints proposed for unidirectional plane waves by Bondi, Pirani, and Robinson (BPR). It is argued that the quantum BPR constraints will predict unidirectionality reliably only for solutions which are semiclassical in a certain sense. The ADM energy and area operators are likely to have imaginary eigenvalues, unless one either shifts to a real connection, or allows the connection to occur other than in a holonomy. In classical theory, the area can evolve to zero. A quantum mechanical mechanism is proposed which would prevent this collapse.Comment: 54 pages; LaTe

    4D Imaging and Diffraction Dynamics of Single-Particle Phase Transition in Heterogeneous Ensembles

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    In this Letter, we introduce conical-scanning dark-field imaging in four-dimensional (4D) ultrafast electron microscopy to visualize single-particle dynamics of a polycrystalline ensemble undergoing phase transitions. Specifically, the ultrafast metal–insulator phase transition of vanadium dioxide is induced using laser excitation and followed by taking electron-pulsed, time-resolved images and diffraction patterns. The single-particle selectivity is achieved by identifying the origin of all constituent Bragg spots on Debye–Scherrer rings from the ensemble. Orientation mapping and dynamic scattering simulation of the electron diffraction patterns in the monoclinic and tetragonal phase during the transition confirm the observed behavior of Bragg spots change with time. We found that the threshold temperature for phase recovery increases with increasing particle sizes and we quantified the observation through a theoretical model developed for single-particle phase transitions. The reported methodology of conical scanning, orientation mapping in 4D imaging promises to be powerful for heterogeneous ensemble, as it enables imaging and diffraction at a given time with a full archive of structural information for each particle, for example, size, morphology, and orientation while minimizing radiation damage to the specimen

    Quasi-continuous Interpolation Scheme for Pathways between Distant Configurations

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    A quasi-continuous interpolation (QCI) scheme is introduced for characterizing physically realistic initial pathways from which to initiate transition state searches and construct kinetic transition networks. Applications are presented for peptides, proteins, and a morphological transformation in an atomic cluster. The first step in each case involves end point alignment, and we describe the use of a shortest augmenting path algorithm for optimizing permutational isomers. The QCI procedure then employs an interpolating potential, which preserves the covalent bonding framework for the biomolecules and includes repulsive terms between unconstrained atoms. This potential is used to identify an interpolating path by minimizing contributions from a connected set of images, including terms corresponding to minima in the interatomic distances between them. This procedure detects unphysical geometries in the line segments between images. The most difficult cases, where linear interpolation would involve chain crossings, are treated by growing the structure an atom at a time using the interpolating potential. To test the QCI procedure, we carry through a series of benchmark calculations where the initial interpolation is coupled to explicit transition state searches to produce complete pathways between specified local minima.This work was supported by the Engineering and Physical Sciences Research Council [grant number EP/H042660/1]This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in the Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review. To access the final edited and published work see http://dx.doi.org/10.1021/ct300483

    The Future of Psychotherapy in Turkey: Predictions for the Next 10 Years

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    Making realistic predictions about the future is important in clinical psychology as in many other disciplines. This opinion survey aimed to examine clinical psychologists' predictions for the next 10 years regarding the status of psychotherapy in Turkey in two stages, with 107 participants in one and 69 in the other. The results revealed that the techniques predicted to increase the most in the next decade were the use of eclectic therapy, mindfulness therapy, solution-focused therapy, system/family approaches, and cognitive-behavioral therapy. Among the therapeutic interventions expected to increase in popularity were Internet-based programs, smartphone applications, and problem solving. In terms of type of psychotherapists, family counselors with certificate/graduate degrees and Internet-based treatment programs were expected to become more common, whereas it was considered that shorter treatment formats and crisis intervention approaches would be preferred. In sum, the present findings provide a current overview for Turkey and a comparison with other literature findings. © 2018 Wolters Kluwer Health, Inc. All rights reserved

    Subsurface Charge Repulsion of Adsorbed H-Adatoms on TiO 2

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    We have used noncontact atomic force microscopy (NC-AFM) and Kelvin probe force microscopy (KPFM) to directly visualize the presence of charged subsurface impurities on rutile TiO2(110). The subsurface charges add an additional electrostatic force between the sample and tip so that they appear as hillocks in the NC-AFM topography. Analysis of several subsurface defects in the same NC-AFM image reveals that the hillocks have discrete heights, which means that defects at different subsurface levels can be detected and distinguished. H adatoms, which are positively charged at the TiO2(110) surface, were found to be repelled by the buried positive charge, so that they form a ∼80–120 Å wide hydrogen-free zone around the charge. Thus, there is an opportunity to deliberately add dopants in order to exclude or perhaps even to confine certain adsorbates to a local region at the surface
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