13 research outputs found

    Applications of advanced transport aircraft in developing countries

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    Four representative market scenarios were studied to evaluate the relative performance of air-and surface-based transportation systems in meeting the needs of two developing contries, Brazil and Indonesia, which were selected for detailed case studies. The market scenarios were: remote mining, low-density transport, tropical forestry, and large cargo aircraft serving processing centers in resource-rich, remote areas. The long-term potential of various aircraft types, together with fleet requirements and necessary technology advances, is determined for each application

    Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

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    PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). RESULTS: ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. CONCLUSION: These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance

    Ubiquitinylated proteins

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    A method of inducing a specific immune response in a mammal, comprising: providing a first composition comprising isolated ubiquitinylated proteins in solution in the absence of membrane bound organelles, the isolated ubiquitinylated proteins comprising one or more specific antigens, and further comprising a threshold quantity of polyubiquitinylated short-lived proteins and polyubiquitinylated defective ribosomal products. The isolated ubiquitinylated proteins are affinity-purified from tumor-derived cells grown in culture, the tumor-derived cells being inhibited from degrading ubiquitinylated proteins via the proteasome while being grown in culture. In this way, highly immunogenic short-lived proteins and defective ribosomal products may be loaded onto dendritic cells for cross-presentation and priming of antigen-specific T cells restricted by either classical or non-classical MHC

    High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery.

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    OBJECTIVE: This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes. STUDY DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery ( or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery ( or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor
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