67 research outputs found

    Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

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    A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients

    Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

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    Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident

    Bactericidal Action of Photogenerated Singlet Oxygen from Photosensitizers Used in Plaque Disclosing Agents

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    Photodynamic therapy (PDT) has been suggested as an efficient clinical approach for the treatment of dental plaque in the field of dental care. In PDT, once the photosensitizer is irradiated with light of a specific wavelength, it transfers the excitation energy to molecular oxygen, which gives rise to singlet oxygen., a major causative pathogen of caries, followed by erythrosine and phloxine, both of which showed activity similar to each other. One of the reasons for the discrepancy between the singlet oxygen generating ability and bactericidal activity was the incorporation efficiency of the photosensitizers into the bacterial cells. The incorporation rate of rose bengal was the highest among the three photosensitizers examined in the present study, likely leading to the highest bactericidal activity. Meanwhile, the addition of L-histidine, a singlet oxygen quencher, cancelled the bactericidal activity of any of the three photoactivated photosensitizers, proving that singlet oxygen was responsible for the bactericidal action.It is strongly suggested that rose bengal is a suitable photosensitizer for the plaque disclosing agents as compared to the other two photosensitizers, phloxine and erythrosine, when used for PDT

    A Study On The Model Of Profit And Risk In Xiamen’s Commercial Banks

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    随着相对滞后的金融体制改革提上议事日程,金融业中的银行业的风险和效益的矛盾对立统一日益成为讨论的焦点、热点。加入WTO对金融业意味着拥有先进管理技术和经验的外资银行抢滩国内银行业务,其对国内中资银行的竞争和生存环境的影响是巨大且不可预测的。作者认为国内中资银行是缺乏效率的,为避免银行命脉被外资控制,国内中资银行不能讳疾忌医,而要以有容乃大、自省的态度积极寻求市场经济下的解决之道,最可取的莫过于解剖一只麻雀。 按照这一思路,本文选取了厦门8家经营较稳定的商业银行进行收益风险模式比较,为国内其他中资商业银行的经营管理提供实证参考。 第一章导言。对银行经营活动的一般特点进行描述。提出银行作为经济...Owing to the combination between banking and economics , influencing factor is increasingly complicated. Banker needs to design one macroanalysis model to logically judge different kinds of income chance and danger all banks faced with,through which banker may supply effective diagnose for banking operating management. The theses takes banking 'data in Xiamen as an example .It exists that huge c...学位:工商管理硕士院系专业:管理学院工商管理教育中心_工商管理硕士(MBA)学号:19981505

    Direct fast heating efficiency of a counter-imploded core plasma employing a laser for fast ignition experiments (LFEX)

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    Fast heating efficiency when a pre-imploded core is directly heated with an ultraintense laser (heating laser) was investigated. \u27Direct heating\u27 means that a heating laser hits a pre-imploded core without applying either a laser guiding cone or an external field. The efficiency, η, is defined as the increase in the internal core energy divided by the energy of the heating laser. Six beams (output of 1.6 kJ) from the GEKKO XII (GXII) green laser system at the Institute of Laser Engineering (ILE), Osaka University were applied to implode a spherical deuterated polystyrene (CD) shell target to form a dense core. The DD-reacted protons and the core x-ray emissions showed a core density of 2.8 ± 0.7 g cm−3, or 2.6 times the solid density. Furthermore, DD-reacted thermal neutrons were utilized to estimate the core temperature between 600 and 750 eV. Thereafter, the core was directly heated by a laser for fast-ignition experiments (LFEX, an extremely energetic ultrashort pulse laser) at ILE with its axis lying along or perpendicular to the GXII bundle axis, respectively. The former and latter laser configurations were termed \u27axial\u27 and \u27transverse modes\u27, respectively. The η was estimated from three independent methods: (1) the core x-ray emission, (2) the thermal neutron yield, and (3) the runaway hot electron spectra. For the axial mode, 0.8%< η <2.1% at low power (low LFEX energy) and 0.4%< η <2.5% at high power (high LFEX energy). For the transverse mode, 2.6%< η <7% at low power and 1.5%< η <7.7% at high power. Their efficiencies were compared with that in the uniform implosion mode using 12 GXII beams, 6% < η <12%, which appeared near to the η for the transverse mode, except that the error bar is very large

    Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

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    无线传感器网络,作为全球未来十大技术之一,集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术,可实时感知、采集、处理、传输网络分布区域内的各种信息数据,在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议,并针对大规模的无线传感器网络设计了一种树状路由协议,它根据节点地址信息来形成路由,从而简化了复杂繁冗的路由表查找和维护,节省了不必要的开销,提高了路由效率,实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR(AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位:工学硕士院系专业:信息科学与技术学院通信工程系_通信与信息系统学号:2332007115216

    Cellular autofluorescence following ionizing radiation.

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    Cells often autofluoresce in response to UV radiation excitation and this can reflect critical aspects of cellular metabolism. Here we report that many different human and murine cell types respond to ionizing radiation with a striking rise in autofluorescence that is dependent on dose and time. There was a highly reproducible fluorescent shift at various wavelengths, which was mirrored by an equally reproducible rise in the vital intracellular metabolic co-factors FAD and NADH. It appears that mitochondria, metabolism and Ca(2+) homeostasis are important for this to occur as cells without mitochondria or cells unable to alter calcium levels did not behave in this way. We believe these radiation-induced changes are of biological importance and that autofluorescence may even provide us with a tool to monitor radiation responses in the clinic
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