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排序方式: 共有1312条查询结果,搜索用时 234 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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3.
Sugawara F. Aoki K. Yamaguchi H. Sasaki K. Sasaki T. Fujisaki H. 《Electron Device Letters, IEEE》1997,18(10):483-485
A new lateral MOS-gated thyristor, called the Base-Current-Controlled Thyristor, is described. This device is designed so that most holes at the on-stage reach the P base through the floating P+ region adjacent to the P base and the on-state MOSFET. At the turn-off stage, the interruption of the hole current to the P base due to switching off the above MOSFET occurs simultaneously with the conventional turn-off operation. The concept of this device is verified experimentally by using the fabricated lateral device with the external MOSFET. This device exhibits a better trade-off relation between the on-state voltage and the turn-off time compared uith the conventional MOS-gated thyristor 相似文献
4.
K Takeda K Saito K Makino Y Saito S Aoki T Koji K Matsumura Y Nomura T Kitano T Nakagawa 《Canadian Metallurgical Quarterly》1997,38(4):559-563
Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro. 相似文献
5.
Masatsune Kato Takaaki Aoki Takashi Noji Yasuhiro Ono Yoji Koike Tomoyuki Hikita Yoshitami Saito 《Journal of Superconductivity and Novel Magnetism》1994,7(1):37-38
We have investigated the relation between the crystal structure and superconductivity in La1.9Bi0.1CuO4+δ , in which the phase separation observed in La2CuO4+δ is suppressed. A phase diagram in theT?δ plane is given for La1.9Bi0.1CuO4+δ with excess oxygen. For very smallδ values, the crystal structure is orthorhombic, and an orthorhombic-tetragonal phase transition occurs markedly atδ ~ 0.03 in the measured temperature range between 13 and 293 K. Superconductivity is observed in the range of 0.04<δ<0.11. This is clear evidence thathigh-T c superconductivity also appears in the tetragonal phase. 相似文献
6.
E Orgnero de Gaisán C Maldonado MF Diaz Gavier A Aoki 《Canadian Metallurgical Quarterly》1997,179(5):453-460
A bioassay system for rapid detection of carcinogenic agents has been developed using male Fischer 344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system, called the medium-term liver bioassay, is fundamentally based on the 2-stage hypothesis of tumor production, employing initiation by diethylnitrosamine (200 mg/kg, i.p.) in the first stage and test chemical administration during the second, in combination with two-thirds partial hepatectomy. It requires only 8 wk for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in our laboratory. Among 63 chemicals that were proved to be carcinogenic in the liver of rat and/or mouse, 57 (90%) gave positive results irrespective of their mutagenicity. Negative compounds include peroxisome proliferators and tamoxifen. Even nonhepatocarcinogens were positive at a rate of 24%. Eighty-six percent (12/14) of mouse liver carcinogens were also positive. On the other hand, only 2 out of 45 noncarcinogens showed very weak positivity. Thus, the efficacy of the system for hepatocarcinogens has been well established. This bioassay is increasingly regarded as an appropriate alternative test for carcinogenicity risk assessment and is practically used for a rapid evaluation of hepatocarcinogenicity of chemicals. 相似文献
7.
Over 2000 electrocution deaths were identified among U.S. construction workers from 1980 to 1991, with the highest mean annual crude mortality rate (2.5 per 100,000 people), and second highest mean age-adjusted rate (2.7 per 100,000 people) of all industries. Although the crude fatality rates showed a downward trend, construction workers are still about four times more likely to be electrocuted at work than are workers in all industries combined. Nearly 40% of the 5083 fatal electrocutions in all industries combined occurred in construction, and 80% were associated with industrial wiring, appliances, and transmission lines. Electrocutions ranked as the second leading cause of death among construction workers, accounting for an average of 15% of traumatic deaths in the industry from 1980 to 1991. The study indicates that the workers most at risk of electrical injury are male, young, nonwhite, and electricians, structural metal workers, and laborers. The most likely time of injury is 11 a.m. to 3 p.m. from June to August. Focusing prevention on these populations and characteristics through better methods of worker and supervisor electrical safety training, use of adequate protective clothing, and compliance with established procedures could minimize the average annual loss of 168 U.S. construction workers. 相似文献
8.
K Okawa T Aoki K Sano S Harihara A Kitano T Kuroki 《Canadian Metallurgical Quarterly》1998,93(12):2405-2410
OBJECTIVE: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. METHODS: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. RESULTS: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. CONCLUSION: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis. 相似文献
9.
Copper phthalocyanine as corrosion inhibitor for ASTM A606-4 steel in 16% hydrochloric acid 总被引:2,自引:0,他引:2
A study based on the corrosion inhibition properties of copper phthalocyanine is described. Coverage degrees of copper phthalocyanine (Cu-phcy) on ASTM-A606-4 steel, obtained by weight loss measurements, were fitted to Langmuir, Frumkin, Temkin and Flory–Huggins adsorption isotherms. A better fit to the Langmuir isotherm was obtained. The polarization curves showed that polarization of both the anodic and cathodic reactions were verified for concentrations higher than 10–4 M, indicating a mixed type action. Only the anodic reactions were polarized for lower concentrations. At high frequencies the Nyquist diagrams showed one capacitive loop attributable to double layer charging and a small one at intermediary frequencies attributable to the faradaic process of hydrogen evolution. The formation of an adsorbed film was characterized by increasing charge transfer resistance values in the low frequency range for increasing inhibitor concentrations. According to the techniques used in this study, copper phthalocyanines showed a high corrosion inhibiting efficiency for all concentrations. 相似文献
10.
The extended Aharonov-Bohm period test, recently proposed by the present authors, is used to study the electron pairing transition in the t-J ladders. The critical point is detected as a gap opening in the extended spectral flow. The result suggests a pairing prior to the onset of a phase separation, which is consistent with a recent Tomonaga-Luttinger analysis. 相似文献