RESUMEN
For coupled structures surrounded by heavy fluids, it is difficult to obtain dispersion curves from an eigenvalue analysis, because the external fluid term in the coupled equation includes transcendental functions for frequency and wavenumber. Thus, in this study, the acoustic mass of the external fluid was approximated as a function of frequency or wavenumber only. The coupled equation can then be used to calculate eigenvalues, and can estimate dispersion curves from an eigenvalue analysis. Because of this assumption, those dispersion curves will contain errors. Accordingly, those errors were evaluated in this study through a comparison with a dispersion curve derived from forced responses. The acoustic mass was also evaluated for a water-loaded plate; this can be formulated theoretically. As a result, the acoustic mass is less sensitive to frequency changes than wavenumber changes, and using the fluid term defined at a low frequency has advantages when estimating the dispersion curve. Finally, the generality of the proposed method was identified through the application for a submerged cylindrical shell.
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Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.
Asunto(s)
Carcinoma Hepatocelular/terapia , Proteínas de Ciclo Celular/genética , Terapia Genética , Proteínas de Homeodominio/genética , Neoplasias Hepáticas/terapia , Viroterapia Oncolítica , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Proteínas Supresoras de Tumor/genética , Animales , Apoptosis , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Efecto Citopatogénico Viral , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ratones , Ratones Desnudos , Neovascularización Patológica/prevención & control , Transfección , Microambiente Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Minimizing power loss of a neutral beam imposes modification of the accelerator of the ion source for further improvement of the beam optics. The beam optics can be improved by focusing beamlets. The injection efficiencies by the steering of ion beamlets are investigated numerically to find the optimum modification of the accelerator design of the NBI-1B ion source. The beam power loss was reduced by aperture displacement of three edge beamlets arrays considering power loadings on the beamline components. Successful testing and operation of the ion source at 60 keV/84% of injection efficiency led to the possibility of enhancing the system capability to a 2.4 MW power level at 100 keV/1.9 µP.
RESUMEN
Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.
Asunto(s)
Translocador 2 del Nucleótido Adenina/metabolismo , Antineoplásicos/metabolismo , Polietileneimina/farmacología , ARN Interferente Pequeño/metabolismo , Animales , Línea Celular Tumoral/efectos de los fármacos , Técnicas de Transferencia de Gen , Xenoinjertos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Ratones , Microburbujas , Trasplante de Neoplasias , ARN Interferente Pequeño/toxicidad , Terapia por UltrasonidoRESUMEN
An internal magnetic probe using Hall sensors to measure a current density profile directly with perturbation of less than 10% to the plasma current is successfully operated for the first time in Versatile Experiment Spherical Torus (VEST). An appropriate Hall sensor is chosen to produce sufficient signals for VEST magnetic field while maintaining the small size of 10 mm in outer diameter. Temperature around the Hall sensor in a typical VEST plasma is regulated by blown air of 2 bars. First measurement of 60 kA VEST ohmic discharge shows a reasonable agreement with the total plasma current measured by Rogowski coil in VEST.
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Volume-produced negative ion source still requires enhancement of current density with lower input RF (radio-frequency) power in lower operating pressure for various applications. To confirm recent observation of efficient negative ion production with a short cylindrical chamber with smaller effective plasma size, the RF-driven transformer-coupled plasma H(-) ion source at Seoul National University is modified by adopting a newly designed quartz RF window to reduce the chamber length. Experiments with the reduced chamber length show a few times enhancement of H(-) ion beam current compared to that extracted from the previous chamber design, which is consistent with the measured H(-) ion population. Nevertheless, decrease in H(-) ion beam current observed in low pressure regime below â¼5 mTorr owing to insufficient filtering of high energy electrons in the extraction region needs to be resolved to address the usefulness of electron temperature control by the change of geometrical configuration of the discharge chamber. A new discharge chamber with conically converging configuration has been developed, in which the chamber diameter decreases as approaching to the extraction region away from the planar RF antenna such that stronger filter magnetic field can be utilized to prohibit high energy electrons from transporting to the extraction region. First experimental results for the H(-) ion beam extraction with this configuration show that higher magnetic filter field makes peak negative beam currents happen in lower operating pressure. However, overall decrease in H(-) ion beam current due to the change of chamber geometry still requires further study of geometrical effect on particle transport and optimization of magnetic field in this novel configuration.
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BACKGROUND: Narcolepsy typically begins between adolescence and early adulthood causing severe neuropsychiatric impairments, but few prevalence studies are available on adolescent narcoleptics. In the present study, we investigated the prevalence of narcolepsy-cataplexy in adolescents. METHODS: In total 20,407 students, aged 14-19 years, participated in this study. Ullanlinna Narcolepsy Scale (UNS) was applied to all subjects and those with a UNS score of > or =14 were contacted by phone for semi-structured interview. Subjects then suspected of having narcolepsy participated in a laboratory investigation, which included polysomnography and HLA typing, or were interviewed in detail by telephone. RESULTS: Three subjects were finally diagnosed as narcolepsy with cataplexy and seven subjects might be diagnosed as narcolepsy without cataplexy. Among three narcoleptics with cataplexy, two subjects were HLA-DQB1*0602 and DRB1*1501 positive, but one subject had no test of HLA typing. The prevalence of narcolepsy with cataplexy in Korean adolescence was thus determined to be 0.015% (95% confidence interval = 0.0-0.0313%). CONCLUSION: This epidemiologic study is the first of its type on adolescent narcolepsy to use the International Classification of Sleep Disorders, 2nd edition (ICSD-2) diagnostic criteria. Considering those cases with an onset after adolescence were not included, the prevalence of narcolepsy with cataplexy determined in the present study is comparable with that of other studies in adults.
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Narcolepsia/diagnóstico , Narcolepsia/epidemiología , Adolescente , Adulto , Edad de Inicio , Pueblo Asiatico , Diagnóstico Diferencial , Femenino , Genotipo , Antígenos HLA/genética , Humanos , Entrevistas como Asunto , Corea (Geográfico)/epidemiología , Masculino , Narcolepsia/fisiopatología , Polisomnografía , Valor Predictivo de las Pruebas , Prevalencia , Encuestas y CuestionariosRESUMEN
We have examined differences in gene expression pattern between embryogenic callus (EC) and nonembryogenic callus (NEC) derived from mature seed embryo of rice (Oryza sativa L. cv Donggin). Three EC-specific transcripts were identified by differential display of amplified cDNAs. Specific expression of two partial cDNAs, designated as REC1 and REC2, respectively, was confirmed by a northern blot analysis. Partial nucleotide sequence of the clone REC1 showed no homology with any known genes, but partial amino acid sequence deduced from the clone REC2 exhibited 55-82% homology with nickel-cobalt-resistant proteins identified from a bacterium, Alcaligenes eutrophus CH34.