620 research outputs found
Particle dynamics of a cartoon dune
The spatio-temporal evolution of a downsized model for a desert dune is
observed experimentally in a narrow water flow channel. A particle tracking
method reveals that the migration speed of the model dune is one order of
magnitude smaller than that of individual grains. In particular, the erosion
rate consists of comparable contributions from creeping (low energy) and
saltating (high energy) particles. The saltation flow rate is slightly larger,
whereas the number of saltating particles is one order of magnitude lower than
that of the creeping ones. The velocity field of the saltating particles is
comparable to the velocity field of the driving fluid. It can be observed that
the spatial profile of the shear stress reaches its maximum value upstream of
the crest, while its minimum lies at the downstream foot of the dune. The
particle tracking method reveals that the deposition of entrained particles
occurs primarily in the region between these two extrema of the shear stress.
Moreover, it is demonstrated that the initial triangular heap evolves to a
steady state with constant mass, shape, velocity, and packing fraction after
one turnover time has elapsed. Within that time the mean distance between
particles initially in contact reaches a value of approximately one quarter of
the dune basis length
Observation of Density Segregation inside Migrating Dunes
Spatiotemporal patterns in nature, such as ripples or dunes, formed by a
fluid streaming over a sandy surface show complex behavior despite their simple
forms. Below the surface, the granular structure of the sand particles is
subject to self-organization processes, exhibiting such phenomena as reverse
grading when larger particles are found on top of smaller ones. Here we report
results of an experimental investigation with downscaled model dunes revealing
that, if the particles differ not in size but in density, the heavier
particles, surprisingly, accumulate in the central core close to the top of the
dune. This finding contributes to the understanding of sedimentary structures
found in nature and might be helpful to improve existing dating methods for
desert dunes.Comment: 4 pages, 5 figures, submitted to Physical Review E Rapid
Communications, in prin
Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
A search for high-energy neutrinos interacting within the IceCube detector
between 2010 and 2012 provided the first evidence for a high-energy neutrino
flux of extraterrestrial origin. Results from an analysis using the same
methods with a third year (2012-2013) of data from the complete IceCube
detector are consistent with the previously reported astrophysical flux in the
100 TeV - PeV range at the level of per flavor and reject a
purely atmospheric explanation for the combined 3-year data at .
The data are consistent with expectations for equal fluxes of all three
neutrino flavors and with isotropic arrival directions, suggesting either
numerous or spatially extended sources. The three-year dataset, with a livetime
of 988 days, contains a total of 37 neutrino candidate events with deposited
energies ranging from 30 to 2000 TeV. The 2000 TeV event is the highest-energy
neutrino interaction ever observed.Comment: 8 pages, 5 figures. Accepted by PRL. The event catalog, event
displays, and other data tables are included after the final page of the
article. Changed from the initial submission to reflect referee comments,
expanding the section on atmospheric backgrounds, and fixes offsets of up to
0.9 seconds in reported event times. Address correspondence to: J. Feintzeig,
C. Kopper, N. Whitehor
Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration
A challenge in using bioactive melt-derived glass in bone regeneration is to produce scaffolds with interconnected pores while maintaining the amorphous nature of the glass and its associated bioactivity. Here we introduce a method for creating porous melt-derived bioactive glass foam scaffolds with low silica content and report in vitro and preliminary in vivo data. The gel-cast foaming process was adapted, employing temperature controlled gelation of gelatin, rather than the in situ acrylic polymerisation used previously. To form a 3D construct from melt derived glasses, particles must be fused via thermal processing, termed sintering. The original Bioglass® 45S5 composition crystallises upon sintering, altering its bioactivity, due to the temperature difference between the glass transition temperature and the crystallisation onset being small. Here, we optimised and compared scaffolds from three glass compositions, ICIE16, PSrBG and 13–93, which were selected due to their widened sintering windows. Amorphous scaffolds with modal pore interconnect diameters between 100–150 µm and porosities of 75% had compressive strengths of 3.4 ± 0.3 MPa, 8.4 ± 0.8 MPa and 15.3 ± 1.8 MPa, for ICIE16, PSrBG and 13–93 respectively. These porosities and compressive strength values are within the range of cancellous bone, and greater than previously reported foamed scaffolds. Dental pulp stem cells attached to the scaffold surfaces during in vitro culture and were viable. In vivo, the scaffolds were found to regenerate bone in a rabbit model according to X-ray micro tomography imaging
Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines
Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention
Eight years after an international workshop on myotonic dystrophy patient registries: case study of a global collaboration for a rare disease.
Background
Myotonic Dystrophy is the most common form of muscular dystrophy in adults, affecting an estimated 10 per 100,000 people. It is a multisystemic disorder affecting multiple generations with increasing severity. There are currently no licenced therapies to reverse, slow down or cure its symptoms. In 2009 TREAT-NMD (a global alliance with the mission of improving trial readiness for neuromuscular diseases) and the Marigold Foundation held a workshop of key opinion leaders to agree a minimal dataset for patient registries in myotonic dystrophy. Eight years after this workshop, we surveyed 22 registries collecting information on myotonic dystrophy patients to assess the proliferation and utility the dataset agreed in 2009. These registries represent over 10,000 myotonic dystrophy patients worldwide (Europe, North America, Asia and Oceania).
Results
The registries use a variety of data collection methods (e.g. online patient surveys or clinician led) and have a variety of budgets (from being run by volunteers to annual budgets over €200,000). All registries collect at least some of the originally agreed data items, and a number of additional items have been suggested in particular items on cognitive impact.
Conclusions
The community should consider how to maximise this collective resource in future therapeutic programmes
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