5,780 research outputs found
Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.
One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA
Enhanced broadband near-IR luminescence and gain spectra of bismuth/erbium co-doped fiber by 830 and 980 nm dual pumping
© 2017 Author(s). A dual 830 and 980 nm pumping scheme is proposed aiming at broadening and flattening the spectral performance of bismuth/erbium codoped multicomponent fiber (BEDF). The spectral properties of distinct Bi active centers (BACs) associated with germanium (BAC-Ge), aluminium (BAC-Al), phosphorus (BAC-P) and silicon (BAC-Si) are characterized under single pumping of 830 and 980 nm, respectively. Based on the emission slope efficiencies of BAC-Al (∼1100 nm) and BAC-Si (∼1430 nm) under single pumping of 830 and 980 nm, the dual pumping scheme with the optimal pump power ratio of 25 (980 nm VS 830 nm) is determined to achieve flat, ultrabroadband luminescence spectra covering the wavelength range 950-1600 nm. The dual pumping scheme is further demonstrated on the on-off gain performance of BEDF. It is found under the pump power ratio of ∼8 (980 VS 830 nm), The gain spectrum has been flattened and broadened over 300 nm (1300-1600 nm) with an average gain coefficient of ∼1.5 dBm-1. The spectral coverage is approximately 1.5 and 3 times wider compared to single pumping of 830 and 980 nm pumping, respectively. The energy level diagrams of 830 and 980 nm are also constructed separately in view of the optical characteristic, which further clarifies the advantage for dual pumping. The proposed dual 830 and 980 nm pumping scheme with the multicomponent BEDF shows great potential in various broadband optical applications such as uniform ASE source, broadband amplifier and tuneable laser in NIR band
The Josephson heat interferometer
The Josephson effect represents perhaps the prototype of macroscopic phase
coherence and is at the basis of the most widespread interferometer, i.e., the
superconducting quantum interference device (SQUID). Yet, in analogy to
electric interference, Maki and Griffin predicted in 1965 that thermal current
flowing through a temperature-biased Josephson tunnel junction is a stationary
periodic function of the quantum phase difference between the superconductors.
The interplay between quasiparticles and Cooper pairs condensate is at the
origin of such phase-dependent heat current, and is unique to Josephson
junctions. In this scenario, a temperature-biased SQUID would allow heat
currents to interfere thus implementing the thermal version of the electric
Josephson interferometer. The dissipative character of heat flux makes this
coherent phenomenon not less extraordinary than its electric (non-dissipative)
counterpart. Albeit weird, this striking effect has never been demonstrated so
far. Here we report the first experimental realization of a heat
interferometer. We investigate heat exchange between two normal metal
electrodes kept at different temperatures and tunnel-coupled to each other
through a thermal `modulator' in the form of a DC-SQUID. Heat transport in the
system is found to be phase dependent, in agreement with the original
prediction. With our design the Josephson heat interferometer yields
magnetic-flux-dependent temperature oscillations of amplitude up to ~21 mK, and
provides a flux-to-temperature transfer coefficient exceeding ~ 60mK/Phi_0 at
235 mK [Phi_0 2* 10^(-15) Wb is the flux quantum]. Besides offering remarkable
insight into thermal transport in Josephson junctions, our results represent a
significant step toward phase-coherent mastering of heat in solid-state
nanocircuits, and pave the way to the design of novel-concept coherent
caloritronic devices.Comment: 4+ pages, 3 color figure
Polarization mode coupling and related effects in fiber Bragg grating inscribed in polarization maintaining fiber
©2016 Optical Society of America. Polarization mode coupling (PMC) and related effects from writing fiber Bragg gratings in polarization maintaining fiber (FBGs-in- PMF) are observed experimentally for the first time by optical fiber coherence domain polarimetry (OCDP) using a broadband light source. PMC is another useful aspect of FBG-in-PMF besides Bragg wavelength and its possible potential is evaluated and discussed. A localized and long range temperature measurement based on the PMC and Bragg wavelength is given as an example
Phosphatidylinositol Transfer Protein-α in platelets is inconsequential for thrombosis yet is utilized for tumor metastasis
Platelets are increasingly recognized for their contributions to tumor metastasis. Here, we show that the phosphoinositide signaling modulated by phosphatidylinositol transfer protein type α (PITPα), a protein which shuttles phosphatidylinositol between organelles, is essential for platelet-mediated tumor metastasis. PITPα-deficient platelets have reduced intracellular pools of phosphoinositides and an 80% reduction in IP3 generation upon platelet activation. Unexpectedly, mice lacking platelet PITPα form thrombi normally at sites of intravascular injuries. However, following intravenous injection of tumor cells, mice lacking PITPα develop fewer lung metastases due to a reduction of fibrin formation surrounding the tumor cells, rendering the metastases susceptible to mucosal immunity. These findings demonstrate that platelet PITPα-mediated phosphoinositide signaling is inconsequential for in vivo hemostasis, yet is critical for in vivo dissemination. Moreover, this demonstrates that signaling pathways within platelets may be segregated into pathways that are essential for thrombosis formation and pathways that are important for non-hemostatic functions
Influence of severe plastic deformation on the precipitation hardening of a FeSiTi steel
The combined strengthening effects of grain refinement and high precipitated
volume fraction (~6at.%) on the mechanical properties of FeSiTi alloy subjected
to SPD processing prior to aging treatment were investigated by atom probe
tomography and scanning transmission electron microscopy. It was shown that the
refinement of the microstructure affects the precipitation kinetics and the
spatial distribution of the secondary hardening intermetallic phase, which was
observed to nucleate heterogeneously on dislocations and sub-grain boundaries.
It was revealed that alloys successively subjected to these two strengthening
mechanisms exhibit a lower increase in mechanical strength than a simple
estimation based on the summation of the two individual strengthening
mechanisms
Future changes in tropical cyclone activity in the North Indian Ocean projected by high-resolution MRI-AGCMs
Open Access at publisher's web site: http://www.springerlink.com/content/b682734237171631
Electronic Origin of High Temperature Superconductivity in Single-Layer FeSe Superconductor
The latest discovery of high temperature superconductivity signature in
single-layer FeSe is significant because it is possible to break the
superconducting critical temperature ceiling (maximum Tc~55 K) that has been
stagnant since the discovery of Fe-based superconductivity in 2008. It also
blows the superconductivity community by surprise because such a high Tc is
unexpected in FeSe system with the bulk FeSe exhibiting a Tc at only 8 K at
ambient pressure which can be enhanced to 38 K under high pressure. The Tc is
still unusually high even considering the newly-discovered intercalated FeSe
system A_xFe_{2-y}Se_2 (A=K, Cs, Rb and Tl) with a Tc at 32 K at ambient
pressure and possible Tc near 48 K under high pressure. Particularly
interesting is that such a high temperature superconductivity occurs in a
single-layer FeSe system that is considered as a key building block of the
Fe-based superconductors. Understanding the origin of high temperature
superconductivity in such a strictly two-dimensional FeSe system is crucial to
understanding the superconductivity mechanism in Fe-based superconductors in
particular, and providing key insights on how to achieve high temperature
superconductivity in general. Here we report distinct electronic structure
associated with the single-layer FeSe superconductor. Its Fermi surface
topology is different from other Fe-based superconductors; it consists only of
electron pockets near the zone corner without indication of any Fermi surface
around the zone center. Our observation of large and nearly isotropic
superconducting gap in this strictly two-dimensional system rules out existence
of node in the superconducting gap. These results have provided an unambiguous
case that such a unique electronic structure is favorable for realizing high
temperature superconductivity
Observation of anomalous decoherence effect in a quantum bath at room temperature
Decoherence of quantum objects is critical to modern quantum sciences and
technologies. It is generally believed that stronger noises cause faster
decoherence. Strikingly, recent theoretical research discovers the opposite
case for spins in quantum baths. Here we report experimental observation of the
anomalous decoherence effect for the electron spin-1 of a nitrogen-vacancy
centre in high-purity diamond at room temperature. We demonstrate that under
dynamical decoupling, the double-transition can have longer coherence time than
the single-transition, even though the former couples to the nuclear spin bath
as twice strongly as the latter does. The excellent agreement between the
experimental and the theoretical results confirms the controllability of the
weakly coupled nuclear spins in the bath, which is useful in quantum
information processing and quantum metrology.Comment: 22 pages, related paper at http://arxiv.org/abs/1102.557
Inferring Binding Energies from Selected Binding Sites
We employ a biophysical model that accounts for the non-linear relationship between binding energy and the statistics of selected binding sites. The model includes the chemical potential of the transcription factor, non-specific binding affinity of the protein for DNA, as well as sequence-specific parameters that may include non-independent contributions of bases to the interaction. We obtain maximum likelihood estimates for all of the parameters and compare the results to standard probabilistic methods of parameter estimation. On simulated data, where the true energy model is known and samples are generated with a variety of parameter values, we show that our method returns much more accurate estimates of the true parameters and much better predictions of the selected binding site distributions. We also introduce a new high-throughput SELEX (HT-SELEX) procedure to determine the binding specificity of a transcription factor in which the initial randomized library and the selected sites are sequenced with next generation methods that return hundreds of thousands of sites. We show that after a single round of selection our method can estimate binding parameters that give very good fits to the selected site distributions, much better than standard motif identification algorithms
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