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排序方式: 共有612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
2.
The three-dimensional morphology of polyethylene single crystals grown from dilute solution has been examined by atomic force microscopy. Single crystals were deposited on a soft ground of aqueous solution of poly(vinyl alcohol) (PVA) to avoid the collapse of thin lamellar crystals with thickness of 10 nm. The observation of single crystals on dried PVA clarifies the morphology of a chair type crystal as well as well-known hollow pyramidal type. It has been confirmed that the screw dislocations in the chair type follow a selection rule of the handedness in a manner to relieve the distortion in the chair type. 相似文献
3.
4.
Hamasaki T. Shinohara Y. Terasawa H. Ochiai K. Hiraoka M. Kanayama H. 《Solid-State Circuits, IEEE Journal of》1996,31(12):1888-1894
The area ratio of analog to digital for mixed-mode chip has been inversely proportional to the process design rule for a given dynamic range objective, in contradiction to the LSI trend. This paper presents a design approach to realize a high degree of size reduction with process design rules for analog circuitry and a signal processing architecture for digital circuitry. A five-level current-mode ΣΔ digital-to-analog converter (DAC) system reveals full scale total harmonic: distortion plus noise (THD+N) of -90 dB and dynamic-range of 100 dB at 3 V (low power of 22 mW). Analog-area down-scaling can be accomplished by this architecture to be 1.09 mm2, using 0.6-μm double-poly double-metal (DPDM) CMOS. For the digital filter, a pipeline instruction sequence with multiplierless architecture also gives small area of 1.98 mm2 相似文献
5.
Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are disorders that are common and disturbing to uremic patients. The treatment of these is problematic. Eight patients on chronic hemodialysis and continuous peritoneal dialysis completed a double-blind placebo-controlled crossover study using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of RLS and sleep disruption. Five patients (62.5%) noted subjective improvement in restless legs symptoms and sleep quality. Objective results were improved only slightly by treatment. The percentage of the first hour in bed during which leg movements occurred decreased from 20.5 +/- 6.0 to 11.5 +/- 3.3, p < 0.05. However, findings during sleep were less positive. The following measures were not significant between placebo and treatment: leg movements per hour of sleep [53.7 +/- 22.3 vs 35.8 +/- 11.8 (p = 0.2)]; and percentage of sleep time spent with leg movements [5.5% +/- 3.2 vs 4.4% +/- 1.4 (p = 0.37)]. Patients continued to have very disrupted sleep, and we could not document an objective improvement in sleep architecture. Thus, although pergolide at the dose of 0.25 mg at bedtime provided subjective improvement in symptoms of restless legs and quality of sleep, and objectively decreased leg movements during the first hour in bed, objectively sleep continued to be disrupted. In this small patient group, the response to pergolide was not uniform, and further investigation is required to test effectiveness at higher doses. 相似文献
6.
The sorption and the permeation of iodine in water-swollen poly(vinyl alcohol) (PVA) membranes and the formation of PVA–iodine complexes were studied. The logarithms of the permeability and the diffusion coefficient decreased approximately linearly with the increase in polymer volume fraction. When the membrane was soaked in an aqueous I2–KI solution, it contracted and Young's modulus increased. These findings were explained in terms of the formation of extra junction points due to the PVA–iodine complexes. These changes were reversible and could be recovered by replacing the solution with water. The length of the polyiodine chain increased with the increase in the degree of hydration of the membrane. At a fixed degree of hydration, Young's modulus of an iodine-sorbed membrane was much greater than that of a membrane soaked in pure water. This finding was explained on the basis of a double-network structure. The extension of the membrane promoted the complex formation, and the complex disappeared when the tension was released. The critical strain necessary for the complex formation was independent of the degree of hydration. The length of polyiodine chain increased with strain and became constant at higher strains. 相似文献
7.
A unique class of conjugated compounds composed of the derivative of condensed polycyclic aromatic compound with the phenyl group and diphenyldiacetylene oligomer was synthesized by annealing of diphenyldiacetylene under elevated pressure. The effect of annealing pressure on the conductivity of the compounds was studied. The total conductivity of the compound decreased with a decrease of frequency, approaching a constant value (dc conductivity: Cdc). The dc conductivity of the compound increased from below 10?15 to 10 S cm?1 with increasing annealing pressure. The dc conductivity of the oligomer was below 10?15 S cm?1 and that of the derivative increased from 10?8 to 10 S cm?1 with decreasing H/C (H/C:0.45–0.04). The conduction of the conjugated compound was electronic. The temperature coefficient of those dc conductivities was positive, with an approximately linear relation between In (CdcT0.5) and (1/T)0.25, where T is the temperature. The ac conductivities Cac were proportional to temperature and frequency f and had the following equation Cac = TfS, S = 0.67–0.75. These results showed that the conduction mechanism can be explained by the hopping in a manifold of states at the Fermi level. © 1994 John Wiley & Sons, Inc. 相似文献
8.
Yoshitsugu Kojima Takashi Ohta Mitsumasa Matsushita Minoru Takahara Toshio Kurauchi 《Polymer Engineering and Science》1992,32(10):686-689
Flat packages (FPs) were formed from epoxy molding compounds with various physical properties using a transfer molding machine. The compounds were prepared by changing kinds and amounts of additives and addition methods. The thermal shock test was carried out by the following procedures. The plastic package was soaked alternately in liquid nitrogen (?196°) and in liquid solder (200°) in the cycle of 140s. The median life to crack initiation was defined to be the cycles when half of the specimens exhibited crack initiation. According to linear fracture mechanics, the following expression was obtained relating the median life N, thermal stress σt, and strength σb; N = C/σ·(σb/σt)m. We found the linear relation between logarithm of Nσ and logarithm of σb/σt for various packages, and estimated the values of C and m as 5 × 104 MPa2 and 5.5, respectively. The value of m was the same as that obtained for a dual-in-line package. 相似文献
9.
The wettability of cement particles is related to the fluidity of cement paste. This paper describes the mechanism of the higher fluidity imparted by the spherical cement particles in light of their wettability. In addition, the effects of gypsum on the wettability were also studied. This study has shown the following: (1) The weight of water and water-reducing agent solution penetrating the spherical cement powder bed is 24-150% higher than that for the ordinary Portland cement powder bed. This results in the improvement of the wettability of the particle surfaces of spherical cement. The high wettability of spherical cement contributes to its high fluidity. (2) The presence of many fine gypsum particles on the spherical cement particle surface reduces the wettability. (3) To prepare spherical cement, the optimum amount of gypsum added is determined by the acceleration of the formation of spherical particles and the wettability of particle surfaces. 相似文献
10.
Yoshitsugu Kosugi Tsutomu Kunieda Naoki Azuma 《Journal of the American Oil Chemists' Society》1994,71(4):445-448
Rice bran oil containing 30–50% free fatty acid was continually converted to an oil containing more than 75% of triacylglycerol
(TG) by means of immobilized lipase. The reaction was carried out at 60°C for 24 h with dehydration and reactant mixing by
dry nitrogen flow under a positive nitrogen atmosphere. Enzymatic TG synthesis with evaporation by heating was not suitable
because of the increasing peroxide value of the oil.
Part of this article was presented at the annual meeting of the Japan Oil Chemists' Society at Sendai, Japan, October, 16,
1990. 相似文献