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  • 1
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    Optical Shaping of X-Ray Free-Electron Lasers (2016)
    American Physical Society (APS)
    Details
    Publication Date: 2016-06-25
    Description: Author(s): A. Marinelli, R. Coffee, S. Vetter, P. Hering, G. N. West, S. Gilevich, A. A. Lutman, S. Li, T. Maxwell, J. Galayda, A. Fry, and Z. Huang In this Letter we report the experimental demonstration of a new temporal shaping technique for x-ray free-electron lasers (FELs). This technique is based on the use of a spectrally shaped infrared (IR) laser and allows optical control of the x-ray generation process. By accurately manipulating the … [Phys. Rev. Lett. 116, 254801] Published Thu Jun 23, 2016
    Keywords: Plasma and Beam Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 2
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    The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family (2016)
    Oxford University Press
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    Publication Date: 2016-05-06
    Description: The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Structure of human {alpha}TAT1 [Biochemistry] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-11-28
    Description: Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Recommended Patient-Reported Core Set of Symptoms to Measure in Prostate Cancer Treatment Trials (2014)
    Oxford University Press
    Details
    Publication Date: 2014-07-10
    Description: The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group’s process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation.
    Electronic ISSN: 1460-2105
    Topics: Medicine
    Published by Oxford University Press
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  • 5
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    Controllable Non-Markovianity for a Spin Qubit in Diamond (2018)
    American Physical Society (APS)
    Details
    Publication Date: 2018-08-11
    Description: Author(s): J. F. Haase, P. J. Vetter, T. Unden, A. Smirne, J. Rosskopf, B. Naydenov, A. Stacey, F. Jelezko, M. B. Plenio, and S. F. Huelga We present a flexible scheme to realize non-Markovian dynamics of an electronic spin qubit, using a nitrogen-vacancy center in diamond where the inherent nitrogen spin serves as a regulator of the dynamics. By changing the population of the nitrogen spin, we show that we can smoothly tune the non-Ma... [Phys. Rev. Lett. 121, 060401] Published Thu Aug 09, 2018
    Keywords: General Physics: Statistical and Quantum Mechanics, Quantum Information, etc.
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 6
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    Developmental regulation of N-terminal H2B methylation in Drosophila melanogaster (2012)
    Oxford University Press
    Details
    Publication Date: 2012-02-28
    Description: Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo . Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other’s activity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Revealing conformational substates of lipidated N-Ras protein by pressure modulation [Biophysics and Computational Biology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-01-12
    Description: Regulation of protein function is often linked to a conformational switch triggered by chemical or physical signals. To evaluate such conformational changes and to elucidate the underlying molecular mechanisms of subsequent protein function, experimental identification of conformational substates and characterization of conformational equilibria are mandatory. We apply pressure modulation in combination with FTIR spectroscopy to reveal equilibria between spectroscopically resolved substates of the lipidated signaling protein N-Ras. Pressure has the advantage that its thermodynamic conjugate is volume, a parameter that is directly related to structure. The conformational dynamics of N-Ras in its different nucleotide binding states in the absence and presence of a model biomembrane was probed by pressure perturbation. We show that not only nucleotide binding but also the presence of the membrane has a drastic effect on the conformational dynamics and selection of conformational substates of the protein, and a new substate appearing upon membrane binding could be uncovered. Population of this new substate is accompanied by structural reorientations of the G domain, as also indicated by complementary ATR-FTIR and IRRAS measurements. These findings thus illustrate that the membrane controls signaling conformations by acting as an effective interaction partner, which has consequences for the G-domain orientation of membrane-associated N-Ras, which in turn is known to be critical for its effector and modulator interactions. Finally, these results provide insights into the influence of pressure on Ras-controlled signaling events in organisms living under extreme environmental conditions as they are encountered in the deep sea where pressures reach the kbar range.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Solving or resolving global tomographic models with spherical wavelets, and the scale and sparsity of seismic heterogeneity (2011)
    Oxford University Press
    Details
    Publication Date: 2011-09-29
    Description: SUMMARY We propose a class of spherical wavelet bases for the analysis of geophysical models and for the tomographic inversion of global seismic data. Its multiresolution character allows for modelling with an effective spatial resolution that varies with position within the Earth. Our procedure is numerically efficient and can be implemented with parallel computing. We discuss two possible types of discrete wavelet transforms in the angular dimension of the cubed sphere. We describe benefits and drawbacks of these constructions and apply them to analyse the information in two published seismic wave speed models of the mantle, using the statistics of wavelet coefficients across scales. The localization and sparsity properties of wavelet bases allow finding a sparse solution to inverse problems by iterative minimization of a combination of the ℓ 2 norm of the data residuals and the ℓ 1 norm of the model wavelet coefficients. By validation with realistic synthetic experiments we illustrate the likely gains from our new approach in future inversions of finite-frequency seismic data.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 9
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    Design of a 400 kV deep underground, high detector efficiency, high target density, high beam intensity accelerator facility (2011)
    American Physical Society (APS)
    Details
    Publication Date: 2011-10-05
    Description: Author(s): A. Lemut, M. Couder, D. Winklehner, U. Greife, A. Hodgkinson, D. Leitner, M. Leitner, J. S. Saba, P. A. Vetter, W. L. Waldron, and M. Wiescher [Phys. Rev. ST Accel. Beams 14, 100101] Published Tue Oct 04, 2011
    Keywords: Low- and Intermediate-Energy Accelerators
    Electronic ISSN: 1098-4402
    Topics: Physics
    Published by American Physical Society (APS)
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  • 10
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    Flagellin Perception Varies Quantitatively in Arabidopsis thaliana and Its Relatives (2012)
    Oxford University Press
    Details
    Publication Date: 2012-05-16
    Description: Much is known about the evolution of plant immunity components directed against specific pathogen strains: They show pervasive functional variation and have the potential to coevolve with pathogen populations. However, plants are effectively protected against most microbes by generalist immunity components that detect conserved pathogen-associated molecular patterns (PAMPs) and control the onset of PAMP-triggered immunity. In Arabidopsis thaliana , the receptor kinase flagellin sensing 2 (FLS2) confers recognition of bacterial flagellin (flg22) and activates a manifold defense response. To decipher the evolution of this system, we performed functional assays across a large set of A. thaliana genotypes and Brassicaceae relatives. We reveal extensive variation in flg22 perception, most of which results from changes in protein abundance. The observed variation correlates with both the severity of elicited defense responses and bacterial proliferation. We analyzed nucleotide variation segregating at FLS2 in A. thaliana and detected a pattern of variation suggestive of the rapid fixation of a novel adaptive allele. However, our study also shows that evolution at the receptor locus alone does not explain the evolution of flagellin perception; instead, components common to pathways downstream of PAMP perception likely contribute to the observed quantitative variation. Within and among close relatives, PAMP perception evolves quantitatively, which contrasts with the changes in recognition typically associated with the evolution of R genes.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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