126 research outputs found
High-fidelity quantum driving
The ability to accurately control a quantum system is a fundamental
requirement in many areas of modern science such as quantum information
processing and the coherent manipulation of molecular systems. It is usually
necessary to realize these quantum manipulations in the shortest possible time
in order to minimize decoherence, and with a large stability against
fluctuations of the control parameters. While optimizing a protocol for speed
leads to a natural lower bound in the form of the quantum speed limit rooted in
the Heisenberg uncertainty principle, stability against parameter variations
typically requires adiabatic following of the system. The ultimate goal in
quantum control is to prepare a desired state with 100% fidelity. Here we
experimentally implement optimal control schemes that achieve nearly perfect
fidelity for a two-level quantum system realized with Bose-Einstein condensates
in optical lattices. By suitably tailoring the time-dependence of the system's
parameters, we transform an initial quantum state into a desired final state
through a short-cut protocol reaching the maximum speed compatible with the
laws of quantum mechanics. In the opposite limit we implement the recently
proposed transitionless superadiabatic protocols, in which the system perfectly
follows the instantaneous adiabatic ground state. We demonstrate that
superadiabatic protocols are extremely robust against parameter variations,
making them useful for practical applications.Comment: 17 pages, 4 figure
N-Cadherin Expression Level Distinguishes Reserved versus Primed States of Hematopoietic Stem Cells
SummaryOsteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherinhi) are not stem cells, being largely devoid of a Lineage−Sca1+cKit+ population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherinint) or low (N-cadherinlo) levels. The minority N-cadherinlo population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherinint population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherinint cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations
Infrared seeded parametric four-wave mixing for sensitive detection of molecules
We have developed a sensitive resonant four-wave mixing technique based on two-photon parametric four-wave mixing with the addition of a phase matched ''seeder'' field. Generation of the seeder field via the same four-wave mixing process in a high pressure cell enables automatic phase matching to be achieved in a low pressure sample cell. This arrangement facilitates sensitive detection of complex molecular spectra by simply tuning the pump laser. We demonstrate the technique with the detection of nitric oxide down to concentrations more than 4 orders of magnitude below the capability of parametric four-wave mixing alone, with an estimated detection threshold of 10(12) molecules/cm(3)
Sensitive detection of sodium in a flame using parametric four-wave mixing and seeded parametric four-wave mixing
Two-photon resonant parametric four-wave mixing and a newly developed variant called seeded parametric four-wave mixing are used to detect trace quantities of sodium in a flame. Both techniques are simple, requiring only a single laser to generate a signal beam at a different wavelength which propagates collinearly with the pump beam, allowing efficient signal recovery. A comparison of the two techniques reveals that seeded parametric four-wave mixing is more than two orders of magnitude more sensitive than parametric four-wave mixing, with an estimated detection sensitivity of 5 x 10(9) atoms/cm(3). Seeded parametric four-wave mixing is achieved by cascading two parametric four-wave mixing media such that one of the parametric fields generated in the first high-density medium is then used to seed the same four-wave mixing process in a second medium in order to increase the four-wave mixing gain. The behavior of this seeded parametric four-wave mixing is described using semiclassical perturbation theory. A simplified small-signal theory is found to model most of the data satisfactorily. However, an anomalous saturationlike behavior is observed in the large signal regime. The full perturbation treatment, which includes the competition between two different four-wave mixing processes coupled via the signal field, accounts for this apparently anomalous behavior
DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia
Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML)
pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures
with defined genomic rearrangements in acute myeloid leukemia are required.
Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we
validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated
with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1
was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced
in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures.
To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/
progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying
the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the
MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the
epigenetic signature observed in the patients.
Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers
for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the
methylation signatur
Nanometer scale thermal response of polymers to fast thermal perturbations
© 2018 Author(s). Nanometer scale thermal response of polymers to fast thermal perturbations is described by linear integro-differential equations with dynamic heat capacity. The exact analytical solution for the non-equilibrium thermal response of polymers in plane and spherical geometry is obtained in the absence of numerical (finite element) calculations. The solution is different from the iterative method presented in a previous publication. The solution provides analytical relationships for fast thermal response of polymers even at the limit t → 0, when the application of the iterative process is very problematic. However, both methods give the same result. It was found that even fast (ca. 1 ns) components of dynamic heat capacity greatly enhance the thermal response to local thermal perturbations. Non-equilibrium and non-linear thermal response of typical polymers under pulse heating with relaxation parameters corresponding to polystyrene and poly(methyl methacrylate) is determined. The obtained results can be used to analyze the heat transfer process at the early stages of crystallization with fast formation of nanometer scale crystals
MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199
Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias. Therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of research. Mutations in the MLL gene cause aggressive incurable leukemias. Benito et al. show that MLL leukemias are highly sensitive to BCL-2 inhibitors, especially when combined with drugs that target mutant MLL complex activity
Bistable Percepts in the Brain: fMRI Contrasts Monocular Pattern Rivalry and Binocular Rivalry
The neural correlates of binocular rivalry have been actively debated in recent years, and are of considerable interest as they may shed light on mechanisms of conscious awareness. In a related phenomenon, monocular rivalry, a composite image is shown to both eyes. The subject experiences perceptual alternations in which the two stimulus components alternate in clarity or salience. The experience is similar to perceptual alternations in binocular rivalry, although the reduction in visibility of the suppressed component is greater for binocular rivalry, especially at higher stimulus contrasts. We used fMRI at 3T to image activity in visual cortex while subjects perceived either monocular or binocular rivalry, or a matched non-rivalrous control condition. The stimulus patterns were left/right oblique gratings with the luminance contrast set at 9%, 18% or 36%. Compared to a blank screen, both binocular and monocular rivalry showed a U-shaped function of activation as a function of stimulus contrast, i.e. higher activity for most areas at 9% and 36%. The sites of cortical activation for monocular rivalry included occipital pole (V1, V2, V3), ventral temporal, and superior parietal cortex. The additional areas for binocular rivalry included lateral occipital regions, as well as inferior parietal cortex close to the temporoparietal junction (TPJ). In particular, higher-tier areas MT+ and V3A were more active for binocular than monocular rivalry for all contrasts. In comparison, activation in V2 and V3 was reduced for binocular compared to monocular rivalry at the higher contrasts that evoked stronger binocular perceptual suppression, indicating that the effects of suppression are not limited to interocular suppression in V1
Transplantation of Specific Human Astrocytes Promotes Functional Recovery after Spinal Cord Injury
Repairing trauma to the central nervous system by replacement of glial support
cells is an increasingly attractive therapeutic strategy. We have focused on the
less-studied replacement of astrocytes, the major support cell in the central
nervous system, by generating astrocytes from embryonic human glial precursor
cells using two different astrocyte differentiation inducing factors. The
resulting astrocytes differed in expression of multiple proteins thought to
either promote or inhibit central nervous system homeostasis and regeneration.
When transplanted into acute transection injuries of the adult rat spinal cord,
astrocytes generated by exposing human glial precursor cells to bone
morphogenetic protein promoted significant recovery of volitional foot
placement, axonal growth and notably robust increases in neuronal survival in
multiple spinal cord laminae. In marked contrast, human glial precursor cells
and astrocytes generated from these cells by exposure to ciliary neurotrophic
factor both failed to promote significant behavioral recovery or similarly
robust neuronal survival and support of axon growth at sites of injury. Our
studies thus demonstrate functional differences between human astrocyte
populations and suggest that pre-differentiation of precursor cells into a
specific astrocyte subtype is required to optimize astrocyte replacement
therapies. To our knowledge, this study is the first to show functional
differences in ability to promote repair of the injured adult central nervous
system between two distinct subtypes of human astrocytes derived from a common
fetal glial precursor population. These findings are consistent with our
previous studies of transplanting specific subtypes of rodent glial precursor
derived astrocytes into sites of spinal cord injury, and indicate a remarkable
conservation from rat to human of functional differences between astrocyte
subtypes. In addition, our studies provide a specific population of human
astrocytes that appears to be particularly suitable for further development
towards clinical application in treating the traumatically injured or diseased
human central nervous system
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