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排序方式: 共有269条查询结果,搜索用时 31 毫秒
1.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
2.
Tan W.S. Uren M.J. Houston P.A. Green R.T. Balmer R.S. Martin T. 《Electron Device Letters, IEEE》2006,27(1):1-3
A novel guarded surface leakage test structure is used to isolate the surface and bulk leakage contributions to gate current in AlGaN/GaN HFETs. Passivation with various recipes of SiN/sub x/ always resulted in the commonly observed increase in gate leakage, which was found to be dominated by bulk leakage through the AlGaN. However, high temperature deposited SiN/sub x/ recipes gave a 1-2 orders reduction in surface leakage, whereas low temperature deposition gave an increase. Gate lag measurements were found to correlate closely with the surface leakage component, giving direct evidence that the key device problem of current slump is associated with current flow at the AlGaN surface. 相似文献
3.
F Thonney FL Munier A Balmer G Pescia DF Schorderet 《Canadian Metallurgical Quarterly》1996,85(35):1058-1062
Retinoblastoma, a tumor of the immature retina concerns babies and young infants in particular. They make up for 14% of malignomas in the first years of life. There are two types of retinoblastoma: In the first two alleles of the gene Rb1 must be inactivated sequentially in the same retinoblast cell until this may escape control. In this case the retinoblastoma is always unilateral and unifocal. This is explained by the lower frequency of two mutations in one retinoblast. The other type, however, is inherited: One allele Rb1 is inactivated in all cells of the organism by mutation. The probability that a second mutation arrives in different retinoblasts is thus high. In this case bilateral multifocal tumors develop. Characterization of the Rb1 gene has permitted identification or at least determination of a haplotype in persons at risk. This knowledge is decisive for early recognition of babies at risk and for genetic counselling. 相似文献
4.
5.
Xiaohong Gu Tinh Nguyen Mounira Oudina David Martin Bouchra Kidah Joan Jasmin Aziz Rezig Lipiin Sung Eric Byrd Jonathan W. Martin Derek L. Ho Y. C. Jean 《Journal of Coatings Technology and Research》2005,2(7):547-556
Atomic force microscopy (AFM) has been used to study the morphology and microstructure of an amine-cured epoxy before and
after outdoor exposure. Measurements were made from samples prepared in an essentially CO2-free, H2O-free glove box and from samples prepared in ambient conditions. For those prepared in a CO2-free glove box, AFM imaging was conducted on (1) an unexposed air/coating surface, (2) an unexposed coating bulk, (3) an
unexposed coating/substrate interface, and (4) a field exposed air/coating surface. For samples prepared in ambient conditions,
only the unexposed air/coating surface was investigated. The same regions of the exposed samples were scanned periodically
by the AFM to monitor changes in the surface morphology of the coating as UV exposure progressed. Small angle neutron scattering
and Fourier transform infrared spectroscopy (FTIR) studies were performed to verify the microstructure and to follow chemical
changes during outdoor exposure, respectively. The results have shown that amine blushing, which occurs only under ambient
conditions, had a significant effect on the surface morphology and microstructure of the epoxy. The surface morphology of
the samples prepared under CO2-free, dry conditions was generally smooth and homogeneous. However, the interface and the bulk samples clearly revealed a
two-phase structure consisting of bright nodular domains and dark interstitial regions, indicating an inhomogeneous microstructure.
Such heterogeneous structure of the bulk was in good agreement with results obtained by small angle neutron scattering of
unexposed samples and by AFM phase imaging of the degraded sample surface. The relationship between submicrometer physical
changes and molecular chemical degradation is discussed.
Presented at the 82nd Annual Meeting of the Federation of Societies for Coatings Technology, October 27–29, 2004, in Chicago,
IL. 相似文献
6.
Li-Piin Sung Joan Jasmin Xiaohong Gu Tinh Nguyen Jonathan W. Martin 《Journal of Coatings Technology and Research》2004,1(4):267-276
Laser scanning confocal microscopy (LSCM) has been used to characterize the changes in film thickness and local surface morphology
of polymer coatings during the UV degradation process. With the noninvasive feature of LSCM, one can obtain thickness information
directly and nondestructively at various exposure times without destroying the specimens or deriving the thickness values
from IR measurement by assuming uniform film ablation. Two acrylic polymer coatings were chosen for the study, and the physical
and chemical changes of the two systems at various exposure times were measured and analyzed. Those measurable physical changes
caused by UV exposure include film ablation, formation of pits and other surface defects, and increases in surface roughness.
It was found in both coatings that changes in measured film thickness by LSCM were not correlated linearly to the predicted
thickness loss using the changes in the CH band obtained by the Fourier Transform Infrared (FTIR) spectroscopy measurements
in the later degradation stages. This result suggested it was not a uniform film ablation process during the UV degradation.
At later stages, where surface deformation became severe, surface roughness and profile information using LSCM were also proven
to be useful for analyzing the surface degradation process
Presented at the 81st Annual Meeting of the Federation of Societies for Coatings Technology, November 13–14, 2004 in Philadelphia,
PA. 相似文献
7.
Hongwu Xu Alexandra Navrotsky M. Lou Balmer Yali Su 《Journal of the American Ceramic Society》2002,85(5):1235-1242
The crystal structures for a suite of substituted pollucites with the compositions CsTi x Al1– x Si2 O6+0.5 x , 0 ≤ x ≤ 1, have been determined from Rietveld analysis of powder synchrotron XRD data. Our results indicate that the pollucite end member (CsAlSi2 O6 ) has a tetragonal structure (space group I 41 / a ), whereas all other compositions are cubic (space group Ia 3 d ). The increased symmetry for the titanium-substituted structures is presumably due to the incorporation of additional O2− anions (needed for compensating the charge imbalance between Ti4+ and Al3+ ), which effectively holds open the expanded cubic framework. In situ cooling experiments of the substituted phase CsTi0.1 Al0.9 Si2 O6.05 reveal a displacive transformation to the tetragonal structure at ∼230 K. This transformation is tricritical in nature and is analogous to the tetragonal-to-cubic transition in pollucite on heating. 相似文献
8.
Aziz Rezig Tinh Nguyen David Martin Lipiin Sung Xiaohong Gu Joan Jasmin Jonathan W. Martin 《Journal of Coatings Technology and Research》2006,3(3):173-184
The relationship between chemical degradation and thickness loss of an unpigmented, non UV-stabilized, crosslinked amine-cured
epoxy coating exposed to three UV conditions was investigated. Spin-coated samples having a thickness of approximately 7 μm
on an Si substrate were prepared from a stochiometric mixture of a bisphenol A epoxy resin and a tetra-functional amine curing
agent. Samples were exposed outdoors and to two accelerated laboratory UV environments. Chemical degradation and thickness
loss were measured by transmission Fourier transform infrared spectroscopy (FTIRS) and laser scanning confocal microscopy
(LSCM), respectively. In addition, surface roughness and morphological changes were measured by atomic forcemicrosocopy (AFM)
and LSCM. Substantial chemical degradation, thickness loss, and morpholocal changes occurred in the exposed films, and the
rate of chemical degradation was greater than that due to the thickness loss. This additional chemical loss was attributed
to an inhomogeneous degradation process in which nanoscale localized depressions initiate at certain sites on the surface,
which then enlarge and deepen with exposure time. The results of this study provide a better understanding of the degradation
mechanism and should lead to the development of scientific-based models for predicting the service life of crosslinked amine-cured
epoxy coatings.
Presented at the 82nd Annual Meeting of the Federation of Societies for Coatings Technology, October 27–29, 2004, in Chicago,
IL 相似文献
9.
The inverse problem approach by conjugate gradient with adjoint equations is adapted to the context of a non-isothermal bioprocess, controlled by internal heat generation from microbial oxidation, as could be found in a composting reactor for instance, to determine the heat source from internal temperature measurements. The volumetric heat source is assumed proportional to the rate of consumption of a substrate by a biomass, as described by a Monod model. Computations are performed for Rayleigh numbers equal to 0.25 and 25, for a representative biochemical reaction under typical boundary conditions, for constant and temperature-dependent model parameters. The influence of noisy input data is also considered. It is found that good solutions can be obtained when heat release and diffusion occur over very different time scales. The variation of the model parameters with temperature must be taken into account, but single sensor solutions are possible at relatively small Rayleigh numbers when convection is present. 相似文献
10.
Mari Lou Balmer Fred F. Lange Carlos G. Levi 《Journal of the American Ceramic Society》1994,77(8):2069-2075
Aqueous solutions of zirconium acetate and aluminum nitrate were spray pyrolyzed at 250°C and upquenched to different temperatures to yield metastable solid solutions of composition Zr(1− x ) Alx O(2− x /2) . An amorphous oxide forms first during pyrolysis which subsequently crystallizes as a single phase for x ≤ 0.57 (≤40 mol% Al2 O3 ). The crystallization temperature increased with Al2 O3 content. Electron diffraction, supported by Raman spectroscopy, indicates that the initial phase is tetragonal. At higher temperatures, the initial solid solation partitions to other metastable phases, viz., t -ZrO2 +γ-Al2 O3 , prior to achieving their equilibrium phase assemblage, m -ZrO2 +α-Al2 O3 . Partitioning yields a nanocomposite microstructure with grain sizes of 20–100 nm, compared to the 3 to 5 nm in the initial, single phase. Compositions containing 45 to 50 mol% Al2 O3 concurrently crystallize and partition. The structure selected during crystallization and the partitioning phenomena are discussed in terms of diffusional constraints during crystallization, which are conceptually similar to those operating during rapid solidification. 相似文献