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排序方式: 共有197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.
3.
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
4.
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
5.
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
6.
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
7.
8.
Christiane Jasmin Reinert‐Weiss Holger Baur Sheikh Abdullah Al Nusayer David Duhme Norbert Frühauf 《Journal of the Society for Information Display》2017,25(2):90-97
Conventional adaptive driving beam headlamps are limited in achieving still higher quantities of switchable pixels by the number of LEDs and movable elements needed. In this paper, it is shown that by integrating an active matrix liquid crystal display module, it is possible to realize fully adaptive high‐resolution headlights without mechanical elements and a finite number of LED with 30 k switchable pixels. 相似文献
9.
Saliha Harrach Jasmin Haag Martin Steinbüchel Rita Schrter Ute Neugebauer Jessica Bertrand Giuliano Ciarimboli 《International journal of molecular sciences》2022,23(22)
Tyrosine kinase inhibitors (TKI) such as Masitinib were reported to be useful as therapeutic options in malignant disorders and nonmalignant diseases, like coronavirus disease 2019 (COVID-19). Most kinases must be translocated into targeted cells by the action of specific transport proteins, as they are hydrophilic and not able to cross cell membranes freely. Accordingly, the efficacy of TKI in target cells is closely dependent on the expression of their transporters. Specifically, Masitinib is an organic cation and is expected to interact with organic cation transporters (OCT and Multidrug and Toxin Extrusion proteins—MATE-). The aim of this work was to characterize the interaction of Masitinib with different OCTs. Human embryonic kidney 293 cells stably transfected with murine or human OCT were used for the experiments. The interaction of Masitinib with OCTs was investigated using quenching experiments. The intracellular accumulation of this drug was quantified using high performance liquid chromatography. Our results identified interactions of Masitinib with almost all investigated mouse (m) and human (h) OCTs and hMATE1 and indicated OCT1 and hOCT2 to be especially potent Masitinib translocators across cell membranes. Interestingly, some important differences were observed for the interaction with murine and human OCTs. In the future, investigations concerning further in vitro and in vivo properties of Masitinib and its efficacy related to transporter-related uptake mechanisms under pathophysiological conditions should be performed. Clinical trials in humans and other animals with Masitinib have already shown promising results. However, further research is necessary to understand the disease specific transport mechanisms of Masitinib to contribute to a successful and responsible therapy employment. 相似文献
10.
Moritz Klawitter Ali El-Ayoubi Jasmin Buch Jakob Rüttinger Maximilian Ehrenfeld Eva Lichtenegger Marcel A. Krüger Klaus Mantwill Florestan J. Koll Markus C. Kowarik Per Sonne Holm Ulrike Naumann 《International journal of molecular sciences》2022,23(17)
Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required. 相似文献