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排序方式: 共有385条查询结果,搜索用时 15 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
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This article reports the results of a study conducted to examine the ability of the Situational Outlook Questionnaire (SOQTM) to effectively discern climates that either encourage or discourage creativity and the ability to initiate change in a team setting. The purpose of the study is to examine the concurrent criterion–related validity of the SOQ. The article explores the characteristics in an organisational climate that promote teamwork and some of the tripwires one needs to be aware of in the formation and management of teams. Nine dimensions of the climate for creativity and change as measured by the Situational Outlook Questionnaire are put forward and defined in relation to teams. The methodology and results of the study are reported. The results show that when subjects (N7equals;154) complete the SOQ based on their recollection of a best– and worst–case team experience, the measure is able to consistently and significantly discriminate between the two types of experiences. Conclusions, implications, and areas for future research to further examine the validity of the SOQ are explored. 相似文献
4.
M Wolfgang P Lauer HS Park L Brossay J Hébert M Koomey 《Canadian Metallurgical Quarterly》1998,29(1):321-330
Neisseria gonorrhoeae, the Gram-negative aetiological agent of gonorrhoeae, is one of many mucosal pathogens of man that expresses competence for natural transformation. Expression of this phenotype by gonococci appears to rely on the expression of type IV pili (Tfp), but the mechanistic basis for this relationship remains unknown. During studies of gonococcal pilus biogenesis, a homologue of the PilT family of proteins, required for Tfp-dependent twitching motility in Pseudomonas aeruginosa and social gliding motility in Myxococcus xanthus, was discovered. Like the findings in these other species, we show here that gonococcal PilT mutants constructed in vitro no longer display twitching motility. In addition, we demonstrate that they have concurrently lost the ability to undergo natural transformation, despite the expression of structurally and morphologically normal Tpf. These results were confirmed by the findings that two classes of spontaneous mutants that failed to express twitching motility and transformability carried mutations in PilT. Piliated PilT mutants and a panel of pilus assembly mutants were found to be deficient in sequence-specific DNA uptake into the cell, the earliest demonstrable step in neisserial competence. The PilT-deficient strains represent the first genetically defined mutants that are defective in DNA uptake but retain Tfp expression. 相似文献
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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
7.
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
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.
Production of a combustible for coal-fired power stations based on sewage sludge . This article describes various means of achieving more extensive mechanical dewatering of sewage sludges. The heat content of the sludge solids can become available for combustion processes. The sludge filter cakes obtained by the “CarboSed” process can be disposed of with minimum energy consumption by fluidized bed combustion or be used after appropriate work-up as a combustible in coal-fired power stations with full exploitation of their heat content for generation of steam and electric current. Partial substitution of primary energy sources such as coal and fuel oil by sludge filter cake is feasible in all cases. The processes thus make a contribution to the saving of energy resources and the disposal of sludge. 相似文献