517 research outputs found
Complexation of novel thiomers and insulin to protect against in vitro enzymatic degradation: towards oral insulin delivery.
A significant barrier to oral insulin delivery is its enzymatic degradation in the gut. Nano-sized polymer-insulin polyelectrolyte complexes (PECS) have been developed to protect insulin against enzymatic degradation. Poly(allylamine) (Paa) was trimethylated to yield QPaa. Thiolation of Paa and QPaa was achieved by attaching either N-acetylcysteine (NAC), or thiobutylamidine (TBA) ligands (Paa-NAC/QPaa-NAC and Paa-TBA/QPaa-TBA thiomers). PEC formulations were prepared in Tris buffer (pH 7.4) at various polymer:insulin mass ratios (0.2:1-2:1). PECS were characterised by %transmittance of light and photon correlation spectroscopy. Insulin complexation efficiency and enzyme-protective effect of these complexes was determined by HPLC. Complexation with insulin was found to be optimal at mass ratios of 0.4-1:1 for all polymers. PECS in this mass range were positively-charged (20-40 mV), nanoparticles (50-200 nm), with high insulin complexation efficiency (> 90 %). Complexation with TBA polymers appeared to result in disulphide bridge formation between the polymers and insulin. In vitro enzymatic degradation assays of QPaa, Paa-NAC, and QPaa-NAC PECS showed that they all offered some protection against insulin degradation by trypsin and {esc}ga{esc}s-chymotrypsin, but not from pepsin. QPaa-NAC complexes with insulin are the most promising formulation for future work, given their ability to offer protection against intestinal enzymes. This work highlights the importance of optimising polymer structure in the delivery of proteins
Synthesis, characterisation and in vitro evaluation of novel thiolated derivatives of polyallylamine and quaternised polyallylamine.
Polyallylamine (Paa) was quaternised by methylation of its primary amines using methyl iodide to yield quaternised Paa (QPaa). Average level of polymer quaternisation was determined by elemental analysis and was found to be 72 ± 2mol%. Subsequent thiolation of Paa (15kDa) and QPaa using two different thiolation procedures involving carbodiimide-mediated conjugation to N-acetylcysteine (NAC) and modification of the polymers using 2-iminothiolane hydrochloride yielded their respective NAC and 4-thiobutylamidine (TBA) conjugates: Paa-NAC/QPaa-NAC and Paa-TBA/QPaa-TBA. Estimation of the free thiol content of thiomers by iodometric titration showed that Paa-NAC and QPaa-NAC displayed 60 ± 1.2 and 60 ± 4.3μmol free thiol groups per gram polymer, respectively, while Paa-TBA and QPaa-TBA conjugates displayed 490 ± 18 and 440 ± 21μmol free thiol groups per gram polymer, respectively. Assessment of polymer mucoadhesion using the mucin adsorption assay method revealed that Paa-NAC and Paa-TBA had the best mucoadhesive profile both adsorbing >20% more mucin than the parent polymer Paa. However, thiolation of QPaa was not observed to result in a marked improvement in adsorption of mucin. Also, while other thiolated derivatives were stable in Tris/phosphate buffer pH8 with no change in free thiol content, Paa-TBA solutions displayed in situ crosslinking of free thiol groups to a disulphide network which was evident after 2h. These results show that thiolation of Paa enhanced its mucoadhesive properties, with Paa-TBA also exhibiting in situ gelling properties. Hence, these novel thiolated Paa derivatives exhibit properties which may be useful in facilitating transmucosal drug delivery and controlled drug release
3D Coronal Density Reconstruction and Retrieving the Magnetic Field Structure during Solar Minimum
Measurement of the coronal magnetic field is a crucial ingredient in
understanding the nature of solar coronal phenomena at all scales. We employed
STEREO/COR1 data obtained during a deep minimum of solar activity in February
2008 (Carrington rotation CR 2066) to retrieve and analyze the
three-dimensional (3D) coronal electron density in the range of heights from
1.5 to 4 Rsun using a tomography method. With this, we qualitatively deduced
structures of the coronal magnetic field. The 3D electron density analysis is
complemented by the 3D STEREO/EUVI emissivity in the 195 A band obtained by
tomography for the same CR. A global 3D MHD model of the solar corona was used
to relate the reconstructed 3D density and emissivity to open/closed magnetic
field structures. We show that the density maximum locations can serve as an
indicator of current sheet position, while the locations of the density
gradient maximum can be a reliable indicator of coronal hole boundaries. We
find that the magnetic field configuration during CR 2066 has a tendency to
become radially open at heliocentric distances greater than 2.5 Rsun. We also
find that the potential field model with a fixed source surface (PFSS) is
inconsistent with the boundaries between the regions with open and closed
magnetic field structures. This indicates that the assumption of the potential
nature of the coronal global magnetic field is not satisfied even during the
deep solar minimum. Results of our 3D density reconstruction will help to
constrain solar coronal field models and test the accuracy of the magnetic
field approximations for coronal modeling.Comment: Published in "Solar Physics
Evolution of active and polar photospheric magnetic fields during the rise of Cycle 24 compared to previous cycles
The evolution of the photospheric magnetic field during the declining phase
and minimum of Cycle 23 and the recent rise of Cycle 24 are compared with the
behavior during previous cycles. We used longitudinal full-disk magnetograms
from the NSO's three magnetographs at Kitt Peak, the Synoptic Optical Long-term
Investigations of the Sun (SOLIS) Vector Spectro-Magnetograph (VSM), the
Spectromagnetograph and the 512-Channel Magnetograph instruments, and
longitudinal full-disk magnetograms from the Mt. Wilson 150-foot tower. We
analyzed 37 years of observations from these two observatories that have been
observing daily, weather permitting, since 1974, offering an opportunity to
study the evolving relationship between the active region and polar fields in
some detail over several solar cycles. It is found that the annual averages of
a proxy for the active region poloidal magnetic field strength, the magnetic
field strength of the high-latitude poleward streams, and the time derivative
of the polar field strength are all well correlated in each hemisphere. These
results are based on statistically significant cyclical patterns in the active
region fields and are consistent with the Babcock-Leighton phenomenological
model for the solar activity cycle. There was more hemispheric asymmetry in the
activity level, as measured by total and maximum active region flux, during
late Cycle 23 (after around 2004), when the southern hemisphere was more
active, and Cycle 24 up to the present, when the northern hemisphere has been
more active, than at any other time since 1974. The active region net proxy
poloidal fields effectively disappeared in both hemispheres around 2004, and
the polar fields did not become significantly stronger after this time. We see
evidence that the process of Cycle 24 field reversal has begun at both poles.Comment: Accepted for publication in Solar Physic
Origins of the Ambient Solar Wind: Implications for Space Weather
The Sun's outer atmosphere is heated to temperatures of millions of degrees,
and solar plasma flows out into interplanetary space at supersonic speeds. This
paper reviews our current understanding of these interrelated problems: coronal
heating and the acceleration of the ambient solar wind. We also discuss where
the community stands in its ability to forecast how variations in the solar
wind (i.e., fast and slow wind streams) impact the Earth. Although the last few
decades have seen significant progress in observations and modeling, we still
do not have a complete understanding of the relevant physical processes, nor do
we have a quantitatively precise census of which coronal structures contribute
to specific types of solar wind. Fast streams are known to be connected to the
central regions of large coronal holes. Slow streams, however, appear to come
from a wide range of sources, including streamers, pseudostreamers, coronal
loops, active regions, and coronal hole boundaries. Complicating our
understanding even more is the fact that processes such as turbulence,
stream-stream interactions, and Coulomb collisions can make it difficult to
unambiguously map a parcel measured at 1 AU back down to its coronal source. We
also review recent progress -- in theoretical modeling, observational data
analysis, and forecasting techniques that sit at the interface between data and
theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue
connected with a 2016 ISSI workshop on "The Scientific Foundations of Space
Weather." 44 pages, 9 figure
Demonstration of the temporal matter-wave Talbot effect for trapped matter waves
We demonstrate the temporal Talbot effect for trapped matter waves using
ultracold atoms in an optical lattice. We investigate the phase evolution of an
array of essentially non-interacting matter waves and observe matter-wave
collapse and revival in the form of a Talbot interference pattern. By using
long expansion times, we image momentum space with sub-recoil resolution,
allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure
Kaon Production and Kaon to Pion Ratio in Au+Au Collisions at \snn=130 GeV
Mid-rapidity transverse mass spectra and multiplicity densities of charged
and neutral kaons are reported for Au+Au collisions at \snn=130 GeV at RHIC.
The spectra are exponential in transverse mass, with an inverse slope of about
280 MeV in central collisions. The multiplicity densities for these particles
scale with the negative hadron pseudo-rapidity density. The charged kaon to
pion ratios are and
for the most central collisions. The ratio is lower than the same
ratio observed at the SPS while the is higher than the SPS result.
Both ratios are enhanced by about 50% relative to p+p and +p
collision data at similar energies.Comment: 6 pages, 3 figures, 1 tabl
Meta-analysis identifies seven susceptibility loci involved in the atopic March
Eczema often precedes the development of asthma in a disease course called the a 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified
2D characterization of near-surface V P/V S: surface-wave dispersion inversion versus refraction tomography
International audienceThe joint study of pressure (P-) and shear (S-) wave velocities (Vp and Vs ), as well as their ratio (Vp /Vs), has been used for many years at large scales but remains marginal in near-surface applications. For these applications, and are generally retrieved with seismic refraction tomography combining P and SH (shear-horizontal) waves, thus requiring two separate acquisitions. Surface-wave prospecting methods are proposed here as an alternative to SH-wave tomography in order to retrieve pseudo-2D Vs sections from typical P-wave shot gathers and assess the applicability of combined P-wave refraction tomography and surface-wave dispersion analysis to estimate Vp/Vs ratio. We carried out a simultaneous P- and surface-wave survey on a well-characterized granite-micaschists contact at Ploemeur hydrological observatory (France), supplemented with an SH-wave acquisition along the same line in order to compare Vs results obtained from SH-wave refraction tomography and surface-wave profiling. Travel-time tomography was performed with P- and SH- wave first arrivals observed along the line to retrieve Vtomo p and Vtomo s models. Windowing and stacking techniques were then used to extract evenly spaced dispersion data from P-wave shot gathers along the line. Successive 1D Monte Carlo inversions of these dispersion data were performed using fixed Vp values extracted from Vtomo p the model and no lateral constraints between two adjacent 1D inversions. The resulting 1D Vsw s models were then assembled to create a pseudo-2D Vsw s section, which appears to be correctly matching the general features observed on the section. If the pseudo-section is characterized by strong velocity incertainties in the deepest layers, it provides a more detailed description of the lateral variations in the shallow layers. Theoretical dispersion curves were also computed along the line with both and models. While the dispersion curves computed from models provide results consistent with the coherent maxima observed on dispersion images, dispersion curves computed from models are generally not fitting the observed propagation modes at low frequency. Surface-wave analysis could therefore improve models both in terms of reliability and ability to describe lateral variations. Finally, we were able to compute / sections from both and models. The two sections present similar features, but the section obtained from shows a higher lateral resolution and is consistent with the features observed on electrical resistivity tomography, thus validating our approach for retrieving Vp/Vs ratio from combined P-wave tomography and surface-wave profiling
- …