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排序方式: 共有1469条查询结果,搜索用时 109 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.
Pablo Esquinazi Miguel A. Ramos Reinhard König 《Journal of Low Temperature Physics》2004,135(1-2):27-38
We discuss the strain dependence of the acoustic properties of amorphous metals in both normal and superconducting states, in the temperature range 0.1 mK<T<1 K. A crossover is found when the strain energy is of the order of the effective interaction energy between tunneling systems at the corresponding temperature. Our results provide clear evidence for the interaction between tunneling systems, whose energy is in quantitative agreement with theoretical expectations, and reveal that without the knowledge of the corresponding strain dependences, the measured temperature dependences below ~50 mK of the acoustic properties of disordered solids are rather meaningless. 相似文献
3.
Patricia Mortreau Reinhard Berndt 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》2004,530(3):559-567
The traditional method used to non-destructively determine the uranium enrichment with an NaI detector is based on the “enrichment meter principle” (Progress report LA-4605-MS, Los Alamos National Laboratory, NNM, 1970, p. 19), which involves measuring the intensity of the 186 keV line of 235U by selecting two regions of interest for the peak and the background. This type of method suffers from several limitations, the most limiting of which are the impossibility to make wall thickness correction or to take the inference of foreign radioisotopes into account. The NaIGEM software (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001; Nucl. Instr. and Meth. A 458 (2001) 196) was developed to overcome these limitations by calculating the 186 keV line intensity with a fitting procedure. The code was tested in different measurement conditions on the wide variety of certified samples, in particular, on reprocessed uranium and on depleted material with thick steel filters interposed between the source and the detector. The results are presented to illustrate the performance and limitations of the tested version (A guide for using NaIGEM code, version 1.5 for DOS and Windows, 2001). The general performance is good except in the case of low-enriched uranium in thick containers. 相似文献
4.
5.
The control of hemorrhage in hypothermic patients with platelet and clotting factor depletion is often impossible. Determining the cause of coagulopathic bleeding (CB) will enable physicians to appropriately focus on rewarming, clotting factor repletion, or both. Objective: To determine the contribution of hypothermia in producing CB and ascertain if simultaneous hypothermia and dilutional coagulopathy (DC) interact synergistically. Method: Prothrombin time, partial thromboplastin time, and platelet function were determined at assay temperatures of 29 degrees to 37 degrees C on normal and critically ill, noncoagulopathic (NC) individuals. Dilutional coagulopathy was created using buffered saline and the assays repeated. Results: Hypothermic assay at < or = 35 degrees C significantly prolonged coagulation times. The effect of hypothermia on NC and DC samples was not different. Conclusion: Assays performed at 37 degrees C underestimate coagulopathy in hypothermic patients. The effect of hypothermia on NC and DC is not different, indicating the lack of a synergistic effect. Normalization of clotting requires both rewarming and clotting factor repletion. 相似文献
6.
Selectivity of partial hydrogenation reactions performed in a pore-through-flow catalytic membrane reactor 总被引:2,自引:0,他引:2
The selectivity of partial hydrogenation reactions of unsaturated substrates was studied in a membrane reactor operating at 323 K and 40 bar hydrogen pressure. The reactor system was constructed as a loop of a saturation vessel and a membrane module in which the reaction mixture was resaturated with hydrogen up to 100 times. In a porous membrane made from cross-linked polyacrylic acid palladium nanoparticles were incorporated as catalysts. A well-defined residence time within the membrane was achieved due to a defined pore structure of the membrane and a convective mass flow of the reaction mixture through the membrane. The selectivity for the partially hydrogenated products was investigated as a function of the pore size of the PAA membrane and was compared to commercially available catalysts. Compared to experiments with supported catalysts (Pd/C and Pd/Al2O3) in a slurry and a fixed bed reactor the selectivity for the desired products could be increased by 3% (1-octyne) up to 40% (geraniol). 相似文献
7.
Das Autobahnmautgesetz zeichnet sich durch eine strenge Zweckbindung für die Mautdaten aus. Diese dürfen ausschlie?lich für
die Zwecke des Mautgesetzes erhoben und verarbeitet werden. Diese Vorgabe hat das LG Magdeburg in einem Beschluss richtungsweisend
auch für die Verbindungsdaten der GSM-Kommunikation best?tigt. 相似文献
8.
Friedrich Schne Gerhard Jahreis Gerhard Richter Reinhard Lange 《Journal of the science of food and agriculture》1993,61(2):245-252
In rapeseed meals (RSM) of a conventional (c) or a newly bred (n) variety 117 or 44 mmol glucosinolates and glucosinolate degradation products per kg dry matter were detected. Soaking meals in aqueous myrosinase or copper sulphate solution and subsequent drying reduced the content of antinutrients by more than 90%. Broiler chickens were fed (i) a glucosinolate-free diet, or this diet in which half the soybean meal was replaced by RSM of various origins and treatment; (ii) untreated cRSM; (iii) cRSM treated with myrosinase: (iv) cRSM treated with Cu (v) untreated nRSM; or (vi) nRSM treated with myrosinase. These diets were administered with or without supplementary iodine. Chickens receiving the iodine-deficient diets with myrosinase-treated RSM showed growth depression, incomplete feathering, leg injuries and severe goitre. In the serum T4 could not be detected. Giving myrosinase-treated RSM plus iodine, or giving other RSM diets irrespective of iodine administration, no growth depression was observed. RSM diets without iodine dosage markedly increased thyroid weight: there were no differences between the RSM variants. In contrast to the treatment with myrosinase, in the sera of the chickens fed on untreated RSM or RSM treated with copper T4 could be detected, suggesting that in iodine-deficient conditions differences in serum T4 concentration between RSM groups indicate a differing anti-thyroid activity. With iodine supplementation the RSM had a significant effect on thyroid weight. The largest thyroids (five-fold heavier) were in the animals with myrosinase-treated cRSM. The untreated cRSM and the nRSM trebled or doubled the thyroid weight, and the myrosinase-treated nRSM trebled it. The thyroid weight of chicks fed cRSM treated with copper did not differ significantly from the glucosinolate-free control. There was evidence that heating the myrosinase-treated RMS produced anti-thyroid compounds; these should be identified in further investigations. 相似文献
9.
With the establishment of the Polytechnical Patent Library at the Ilmenau Institute of Technology in April 1981, an efficient patent information centre was set up for the southern districts of the German Democratic Republic (Suhl, Gera, Erfurt). First, the manual methods of search were complemented by two subsystems of the automized patent pre-search system, namely the selective dissemination of information and the field-oriented patent family service. In 1985, the set-up of patent databanks was begun. The present paper explains their specific features, thus complementing the conception of the patent pre-search system presented in previous papers.(1,2) The information services are rendered by order of the Inventions and Patent Office. 相似文献
10.
S. Salar Behzadi Silvester Ölzant Reinhard Länger Christian Koban Frank M. Unger Helmut Viernstein 《European Food Research and Technology》2006,223(2):238-245
Inversion of sucrose is a stability problem particularly of candies with acidic taste that contain sucrose and small amounts of organic acids such as citric acid, since the free d-fructose produced by hydrolysis is hygroscopic. The following possibilities were investigated for preventing the hydrolysis of sucrose in tablets containing sucrose and citric acid: Adding various amounts of tri-sodium citrate to the formulation to neutralize the citric acid, (Hot) melt coating of citric acid and tri-sodium citrate with a vegetable fat at different coating ratios, variation of the ratio of coated citric acid and tri-sodium citrate in formulations, and compressing the formulations with different compression forces. After tablet processing and storage of tablets, the concentration of d-fructose was determined on the basis of enzymatic reactions. A response surface central composite design was used. The above-mentioned variations were chosen as independent variables and the amount of d-fructose was chosen as response variable. The lowest rates of inversion could be achieved by increasing the content of tri-sodium citrate and the ratio of coating material and decreasing the ratio of coated citric acid and tri-sodium citrate in the tablet formulations. The compression force had no significant effect on the inversion of sucrose. 相似文献