3,988 research outputs found
Electrode-induced lattice distortions in GaAs multi-quantum-dot arrays
Copyright © Materials Research Society 2019. Increasing the number of quantum bits while preserving precise control of their quantum electronic properties is a significant challenge in materials design for the development of semiconductor quantum computing devices. Semiconductor heterostructures can host multiple quantum dots that are electrostatically defined by voltages applied to an array of metallic nanoelectrodes. The structural distortion of multiple-quantum-dot devices due to elastic stress associated with the electrodes has been difficult to predict because of the large micrometer-scale overall sizes of the devices, the complex spatial arrangement of the electrodes, and the sensitive dependence of the magnitude and spatial variation of the stress on processing conditions. Synchrotron X-ray nanobeam Bragg diffraction studies of a GaAs/AlGaAs heterostructure reveal the magnitude and nanoscale variation of these distortions. Investigations of individual linear electrodes reveal lattice tilts consistent with a 28-MPa compressive residual stress in the electrodes. The angular magnitude of the tilts varies by up to 20% over distances of less than 200 nm along the length of the electrodes, consistent with heterogeneity in the metal residual stress. A similar variation of the crystal tilt is observed in multiple-quantum-dot devices, due to a combination of the variation of the stress and the complex electrode arrangement. The heterogeneity in particular can lead to significant challenges in the scaling of multiple-quantum-dot devices due to differences between the charging energies of dots and uncertainty in the potential energy landscape. Alternatively, if incorporated in design, stress presents a new degree of freedom in device fabrication
Non-Invasive MRI of Blood-Cerebrospinal Fluid Barrier Function
The blood-cerebrospinal fluid barrier (BCSFB) is a highly dynamic transport interface that serves brain homeostasis. To date, however, understanding of its role in brain development and pathology has been hindered by the absence of a non-invasive technique for functional assessment. Here we describe a method for non-invasive measurement of BSCFB function by using tracer-free MRI to quantify rates of water delivery from arterial blood to ventricular cerebrospinal fluid. Using this method, we record a 36% decrease in BCSFB function in aged mice, compared to a 13% decrease in parenchymal blood flow, itself a leading candidate biomarker of early neurodegenerative processes. We then apply the method to explore the relationship between BCSFB function and ventricular morphology. Finally, we provide proof of application to the human brain. Our findings position the BCSFB as a promising new diagnostic and therapeutic target, the function of which can now be safely quantified using non-invasive MRI
Exploring the Free Energy Landscape: From Dynamics to Networks and Back
The knowledge of the Free Energy Landscape topology is the essential key to
understand many biochemical processes. The determination of the conformers of a
protein and their basins of attraction takes a central role for studying
molecular isomerization reactions. In this work, we present a novel framework
to unveil the features of a Free Energy Landscape answering questions such as
how many meta-stable conformers are, how the hierarchical relationship among
them is, or what the structure and kinetics of the transition paths are.
Exploring the landscape by molecular dynamics simulations, the microscopic data
of the trajectory are encoded into a Conformational Markov Network. The
structure of this graph reveals the regions of the conformational space
corresponding to the basins of attraction. In addition, handling the
Conformational Markov Network, relevant kinetic magnitudes as dwell times or
rate constants, and the hierarchical relationship among basins, complete the
global picture of the landscape. We show the power of the analysis studying a
toy model of a funnel-like potential and computing efficiently the conformers
of a short peptide, the dialanine, paving the way to a systematic study of the
Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press
The central image of a gravitationally lensed quasar
A galaxy can act as a gravitational lens, producing multiple images of a
background object. Theory predicts there should be an odd number of images but,
paradoxically, almost all observed lenses have 2 or 4 images. The missing image
should be faint and appear near the galaxy's center. These ``central images''
have long been sought as probes of galactic cores too distant to resolve with
ordinary observations. There are five candidates, but in one case the third
image is not necessarily a central image, and in the others, the central
component might be a foreground source rather than a lensed image. Here we
report the most secure identification of a central image, based on radio
observations of PMN J1632-0033, one of the latter candidates. Lens models
incorporating the central image show that the mass of the lens galaxy's central
black hole is less than 2 x 10^8 M_sun, and the galaxy's surface density at the
location of the central image is more than 20,000 M_sun per square parsec, in
agreement with expectations based on observations of galaxies hundreds of times
closer to the Earth.Comment: Nature, in press [7 pp, 2 figs]. Standard media embargo applies
before publicatio
Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.
BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse
Issues in the Pharmacokinetics of Trichloroethylene and Its Metabolites
Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE). Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based pharmacokinetic (PBPK) models have led to a better quantitative assessment of the dosimetry of TCE and several of its metabolites. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article is a review of a number of the current scientific issues in TCE pharmacokinetics and recent PBPK modeling efforts with a focus on literature published since 2000. Particular attention is paid to factors affecting PBPK modeling for application to risk assessment. Recent TCE PBPK modeling efforts, coupled with methodologic advances in characterizing uncertainty and variability, suggest that rigorous application of PBPK modeling to TCE risk assessment appears feasible at least for TCE and its major oxidative metabolites trichloroacetic acid and trichloroethanol. However, a number of basic structural hypotheses such as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited treatment of tissue distribution require additional evaluation and analysis. Moreover, there are a number of metabolites of potential toxicologic interest, such as chloral, dichloroacetic acid, and those derived from glutathione conjugation, for which reliable pharmacokinetic data is sparse because of analytical difficulties or low concentrations in systemic circulation. It will be a challenge to develop reliable dosimetry for such cases
A close halo of large transparent grains around extreme red giant stars
Intermediate-mass stars end their lives by ejecting the bulk of their
envelope via a slow dense wind back into the interstellar medium, to form the
next generation of stars and planets. Stellar pulsations are thought to elevate
gas to an altitude cool enough for the condensation of dust, which is then
accelerated by radiation pressure from starlight, entraining the gas and
driving the wind. However accounting for the mass loss has been a problem due
to the difficulty in observing tenuous gas and dust tens of milliarcseconds
from the star, and there is accordingly no consensus on the way sufficient
momentum is transferred from the starlight to the outflow. Here, we present
spatially-resolved, multi-wavelength observations of circumstellar dust shells
of three stars on the asymptotic giant branch of the HR diagram. When imaged in
scattered light, dust shells were found at remarkably small radii (<~ 2 stellar
radii) and with unexpectedly large grains (~300 nm radius). This proximity to
the photosphere argues for dust species that are transparent to starlight and
therefore resistant to sublimation by the intense radiation field. While
transparency usually implies insufficient radiative pressure to drive a wind,
the radiation field can accelerate these large grains via photon scattering
rather than absorption - a plausible mass-loss mechanism for lower-amplitude
pulsating stars.Comment: 13 pages, 1 table, 6 figure
- …