4,356 research outputs found
Identification of neutral tumor evolution across cancer types
A.S. is supported by The Chris Rokos Fellowship in Evolution and Cancer.
B.W. is supported by the Geoffrey W. Lewis Post-Doctoral Training fellowship.
This work was supported by the Wellcome Trust (105104/Z/14/Z). C.P.B.
acknowledges funding from the Wellcome Trust through a Research Career
Development Fellowship (097319/Z/11/Z). This work was supported by a
Cancer Research UK Career Development Award to T.A.G. M.J.W. is supported
by a UK Medical Research Council student fellowship
Magnetic properties of (VO)_2P_2O_7: two-plane structure and spin-phonon interactions
Detailed experiments on single-crystal (VO)_2P_2O_7 continue to reveal new
and unexpected features. We show that a model composed of two, independent
planes of spin chains with frustrated magnetic coupling is consistent with
nuclear magnetic resonance and inelastic neutron scattering measurements. The
pivotal role of PO_4 groups in mediating intrachain exchange interactions
explains both the presence of two chain types and their extreme sensitivity to
certain lattice vibrations, which results in the strong magnetoelastic coupling
observed by light scattering. We compute the respective modifications of the
spin and phonon dynamics due to this coupling, and illustrate their observable
consequences on the phonon frequencies, magnon dispersions, static
susceptibility and specific heat.Comment: 10 pages, 9 figure
Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer
Lacking targetable molecular drivers, triple-negative breast cancer (TNBC) is the most clinically challenging subtype of breast cancer. In this study, we reveal that Death Effector Domain-containing DNA-binding protein (DEDD), which is overexpressed in > 60% of TNBCs, drives a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain of cytosolic DEDD enhances cyclin D1 expression by interacting with heat shock 71 kDa protein 8 (HSC70). Concurrently, DEDD interacts with Rb family proteins and promotes their proteasome-mediated degradation. DEDD overexpression renders TNBCs vulnerable to cell cycle inhibition. Patients with TNBC have been excluded from CDK 4/6 inhibitor clinical trials due to the perceived high frequency of Rb-loss in TNBCs. Interestingly, our study demonstrated that, irrespective of Rb status, TNBCs with DEDD overexpression exhibit a DEDD-dependent vulnerability to combinatorial treatment with CDK4/6 inhibitor and EGFR inhibitor in vitro and in vivo. Thus, our study provided a rationale for the clinical application of CDK4/6 inhibitor combinatorial regimens for patients with TNBC
Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy of GNNQQNY Nanocrystals and Amyloid Fibrils
Dynamic nuclear polarization (DNP) utilizes the inherently larger polarization of electrons to enhance the sensitivity of conventional solid-state NMR experiments at low temperature. Recent advances in instrumentation development and sample preparation have transformed this field and have opened up new opportunities for its application to biological systems. Here, we present DNP-enhanced [superscript 13]C–[superscript 13]C and [superscript 15]N–[superscript 13]C correlation experiments on GNNQQNY nanocrystals and amyloid fibrils acquired at 9.4 T and 100 K and demonstrate that DNP can be used to obtain assignments and site-specific structural information very efficiently. We investigate the influence of temperature on the resolution, molecular conformation, structural integrity and dynamics in these two systems. In addition, we assess the low-temperature performance of two commonly used solid-state NMR experiments, proton-driven spin diffusion (PDSD) and transferred echo double resonance (TEDOR), and discuss their potential as tools for measurement of structurally relevant distances at low temperature in combination with DNP.National Institutes of Health (U.S.) (Grant EB002804)National Institutes of Health (U.S.) (Grant EB003151)National Institutes of Health (U.S.) (Grant EB002026
Thermodynamic properties of the two-dimensional S=1/2 Heisenberg antiferromagnet coupled to bond phonons
By applying a quantum Monte Carlo procedure based on the loop algorithm we
investigate thermodynamic properties of the two-dimensional antiferromagnetic
S=1/2 Heisenberg model coupled to Einstein phonons on the bonds. The
temperature dependence of the magnetic susceptibility, mean phonon occupation
numbers and the specific heat are discussed in detail. We study the spin
correlation function both in the regime of weak and strong spin phonon coupling
(coupling constants g=0.1, w=8J and g=2, w=2J, respectively). A finite size
scaling analysis of the correlation length indicates that in both cases long
range Neel order is established in the ground state.Comment: 10 pages, 13 figure
Multicenter comparison of serum and whole-blood specimens for detection of Aspergillus DNA in high-risk hematological patients
Triplet Dispersion in CuGeO_3: Perturbative Analysis
We reconsider the 2d model for CuGeO_3 introduced previously (Phys. Rev.
Lett. 79, 163 (1997)). Using a computer aided perturbation method based on flow
equations we expand the 1-triplet dispersion up to 10th order. The expansion is
provided as a polynom in the model parameters. The latter are fixed by fitting
the theoretical result to experimental data obtained by INS. For a dimerization
delta = 0.08(1) we find an excellent agreement with experiment. This value is
at least 2 to 3 times higher than values deduced previously from 1d chain
approaches. For the intrachain frustration alpha_0 we find a smaller value of
0.25(3). The existence of interchain frustration conjectured previously is
confirmed by the analysis of temperature dependent susceptibility.Comment: 8 pages, 10 figures, submitted to Phys. Rev.
Persistent fluctuations in stride intervals under fractal auditory stimulation
Copyright @ 2014 Marmelat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.Commission of the European Community and the Netherlands Organisation for Scientific Research
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