Sample records for radiosensitive liquid core
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Liu, Hongmei; Cai, Yifan; Zhang, Yafei; Xie, Yandong; Qiu, Hui; Hua, Lei; Liu, Xuejiao; Li, Yuling; Lu, Jun; Zhang, Longzhen; Yu, Rutong
2017-06-01
Gliomas are highly radioresistant tumors, mainly due to hypoxia in the core region of the gliomas and efficient DNA double-strand break repair. However, the design of a radiosensitizer incorporating the two above mechanisms is difficult and has rarely been reported. Thus, this study develops a hypoxic radiosensitizer-prodrug liposome (MLP) to deliver the DNA repair inhibitor Dbait (MLP/Dbait) to achieve the simultaneous entry of radiosensitizers with two different mechanisms into the glioma. MLP/Dbait effectively sensitizes glioma cells to X-ray radiotherapy (RT). Histological and microscopic examinations of dissected brain tissue confirm that MLP effectively delivers Dbait into the glioma. Furthermore, the combination of MLP/Dbait with RT significantly inhibits growth of the glioma, as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a Dbait delivery system to enhance the effect of RT on glioma, owing to the synergistic effects of the two different radiosensitizers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Fan, Wenpei; Shen, Bo; Bu, Wenbo; Zheng, Xiangpeng; He, Qianjun; Cui, Zhaowen; Zhao, Kuaile; Zhang, Shengjian; Shi, Jianlin
2015-03-01
Clinically applied chemotherapy and radiotherapy is sometimes not effective due to the limited dose acting on DNA chains resident in the nuclei of cancerous cells. Herein, we develop a new theranostic technique of "intranuclear radiosensitization" aimed at directly damaging the DNA within the nucleus by a remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm nuclear-targeting rattle-structured upconversion core/mesoporous silica nanotheranostic system was firstly constructed to directly transport the radiosensitizing drug Mitomycin C (MMC) into the nucleus for substantially enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer treatment as well as multi-drug resistance circumvention in vitro and in vivo . We hope the technique of intranuclear radiosensitization along with the design of nuclear-targeting nanotheranostics will contribute greatly to the development of cancer theranostics as well as to the improvement of the overall therapeutic effectiveness.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo
2009-10-01
Purpose: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. Methods and Materials: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 {mu}g) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl{sub 2} solution supplemented with 0-0.01% yttrium.more » These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy {sup 60}Co {gamma}-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. Results: Microcapsules that had been polymerized using a 4.34% CaCl{sub 2} solution supplemented with 5.0 x 10{sup -3}% (10{sup -3}% meant or 10%{sup -3}) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. Conclusion: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.« less
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[Changes in cellular radiosensitivity after low dose irradiation].
Pelevina, I I; Aleshchenko, A V; Antoshchina, M M; Kudriashova, O V; Riabchenko, N I; Akleev, A V
2012-01-01
When the adaptive response (AR) was studied on human blood lymphocytes, a new dependence was discovered. This dependence defines the direction of the radiosensitivity change after a low dose of irradiation. Using micronucleus (MN) test with cytochalasin B the dependence between the cell reaction after low level irradiation and radiosensititvity (the effect after irradiation at the dose of 1 Gy) was observed. The negative correlation between the frequency of AR manifestation, sensibilization, intermediate links and radiosensitivity was discovered. This regularity is observed in the population of Moscow, Obninsk, Chelyabinsk region (irradiated and control) inhabitants, Chernobyl accident liquidators, Moscow children, in individuals with Hodgkin's lymphoma before and during treatment. The negative correlation is also noted by AR determination with two irradiation schemes: in one or two different cell cycle phases (G1-G1 or G1-G2). Similar links are observed using the chromosome methaphase analysis (the frequency of cells with chromosome aberrations). So, the results of the experiments conducted allow us to suppose that the connection between the cell radiosensitivity and a different type of reaction after low dose irradiation--from AR to the increase in radiosensitivity (sensibilization) is a general regularity. AR is induced by low level irradiation and high cell radiosensitivity, while sensibilization is induced by low radiosensitivity. Since AR and sensibilization can be induced not only by irradiation, but many different chemicals and physical agents, the described correlation can be observed in the case of different exposures. Cellular AR and sensibilization are integral indexes depending on many genetic and epigenetic factors, as well as on the initiation of a large number of events. However, the discovered mechanisms of interrelations are still difficult to explain.
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Flanagan, Sheryl A; Cooper, Kristin S; Mannava, Sudha; Nikiforov, Mikhail A; Shewach, Donna S
2012-12-01
To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and radiosensitization and the mechanism by which these events occur. shRNA suppression of TS was compared with 5-fluoro-2'-deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and radiosensitization were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquid chromatography and as pSP189 plasmid mutations, respectively. TS shRNA produced profound (≥ 90%) and prolonged (≥ 8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting radiosensitization (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. TS shRNA produced less cytotoxicity than FdUrd but was equally effective at radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit radiosensitization with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA mismatches underlying radiosensitization. Importantly, shRNA suppression of TS avoids FP-mediated TS elevation and its negative prognostic role. These studies support the further exploration of TS suppression as a novel radiosensitizing strategy. Copyright © 2012 Elsevier Inc. All rights reserved.
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Jin, Cheng; Bai, Ling; Wu, Hong; Tian, Furong; Guo, Guozhen
2007-09-01
Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The radiosensitization of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles.
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Eady, J. J.; Orta, T.; Dennis, M. F.; Stratford, M. R.; Peacock, J. H.
1995-01-01
Large fluctuations in glutathione content were observed on a daily basis using the Tietze enzyme recycling assay in a panel of six human cell lines of varying radiosensitivity. Glutathione content tended to increase to a maximum during exponential cell proliferation, and then decreased at different rates as the cells approached plateau phase. By reference to high-performance liquid chromatography and flow cytometry of the fluorescent bimane derivative we were able to verify that these changes were real. However, the Tietze assay was occasionally unable to detect glutathione in two of our cell lines (MGH-U1 and AT5BIVA), although the other methods indicated its presence. The existence of an inhibitory activity responsible for these anomalies was confirmed through spiking our samples with known amounts of glutathione. We were unable to detect a direct relationship between cellular glutathione concentration and aerobic radiosensitivity in our panel of cell lines. PMID:7577452
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2013-01-01
Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image contrast, and serve as a radiosensitizer, gold-loaded polymeric micelles (GPMs) were prepared. Specifically, 1.9 nm AuNPs were encapsulated within the hydrophobic core of micelles formed with the amphiphilic diblock copolymer poly(ethylene glycol)-b-poly(ε-capralactone). GPMs were produced with low polydispersity and mean hydrodynamic diameters ranging from 25 to 150 nm. Following intravenous injection, GPMs provided blood pool contrast for up to 24 h and improved the delineation of tumor margins via CT. Thus, GPM-enhanced CT imaging was used to guide radiation therapy delivered via a small animal radiation research platform. In combination with the radiosensitizing capabilities of gold, tumor-bearing mice exhibited a 1.7-fold improvement in the median survival time, compared with mice receiving radiation alone. It is envisioned that translation of these capabilities to human cancer patients could guide and enhance the efficacy of radiation therapy. PMID:24377302
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In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.
Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P
2011-09-01
Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.
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NASA Technical Reports Server (NTRS)
Asaad, N. A.; Zeng, Z. C.; Guan, J.; Thacker, J.; Iliakis, G.
2000-01-01
The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.
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Injector for liquid fueled rocket engine
NASA Technical Reports Server (NTRS)
Cornelius, Charles S. (Inventor); Myers, W. Neill (Inventor); Shadoan, Michael David (Inventor); Sparks, David L. (Inventor)
2000-01-01
An injector for liquid fueled rocket engines wherein a generally flat core having a frustoconical dome attached to one side of the core to serve as a manifold for a first liquid, with the core having a generally circular configuration having an axis. The other side of the core has a plurality of concentric annular first slots and a plurality of annular concentric second slots alternating with the first slots, the second slots having a greater depth than said first slots. A bore extends through the core for inletting a second liquid into said core, the bore intersecting the second slots to feed the second liquid into the second slots. The core also has a plurality of first passageways leading from the manifold to the first annular slots for feeding the first liquid into said first slots. A faceplate brazed to said other side of the core is provided with apertures extending from the first and second slots through said face plate, these apertures being positioned to direct fuel and liquid oxygen into contact with each other in the combustion chamber. The first liquid may be liquid oxygen and the second liquid may be kerosene or liquid hydrogen.
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Core Formation Process and Light Elements in the Planetary Core
NASA Astrophysics Data System (ADS)
Ohtani, E.; Sakairi, T.; Watanabe, K.; Kamada, S.; Sakamaki, T.; Hirao, N.
2015-12-01
Si, O, and S are major candidates for light elements in the planetary core. In the early stage of the planetary formation, the core formation started by percolation of the metallic liquid though silicate matrix because Fe-S-O and Fe-S-Si eutectic temperatures are significantly lower than the solidus of the silicates. Therefore, in the early stage of accretion of the planets, the eutectic liquid with S enrichment was formed and separated into the core by percolation. The major light element in the core at this stage will be sulfur. The internal pressure and temperature increased with the growth of the planets, and the metal component depleted in S was molten. The metallic melt contained both Si and O at high pressure in the deep magma ocean in the later stage. Thus, the core contains S, Si, and O in this stage of core formation. Partitioning experiments between solid and liquid metals indicate that S is partitioned into the liquid metal, whereas O is weakly into the liquid. Partitioning of Si changes with the metallic iron phases, i.e., fcc iron-alloy coexisting with the metallic liquid below 30 GPa is depleted in Si. Whereas hcp-Fe alloy above 30 GPa coexisting with the liquid favors Si. This contrast of Si partitioning provides remarkable difference in compositions of the solid inner core and liquid outer core among different terrestrial planets. Our melting experiments of the Fe-S-Si and Fe-O-S systems at high pressure indicate the core-adiabats in small planets, Mercury and Mars, are greater than the slope of the solidus and liquidus curves of these systems. Thus, in these planets, the core crystallized at the top of the liquid core and 'snowing core' formation occurred during crystallization. The solid inner core is depleted in both Si and S whereas the liquid outer core is relatively enriched in Si and S in these planets. On the other hand, the core adiabats in large planets, Earth and Venus, are smaller than the solidus and liquidus curves of the systems. The inner core of these planets crystallized at the center of the core and it has the relatively Si rich inner core and the S enriched outer core. Based on melting and solid-liquid partitioning, the equation of state, and sound velocity of iron-light element alloys, we examined the plausible distribution of light elements in the liquid outer and solid inner cores of the terrestrial planets.
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Microdosimetric considerations of effects of heavy ions on E. coli K-12 mutants.
Takahashi, T; Yatagai, F; Izumo, K
1992-01-01
The inactivation cross sections of E. coli K-12 recombination-deficient mutants, JC1553 (recA) and AB2470 (recB), for several MeV/u alpha-particles and N ions have been successfully analyzed by Katz's target theory in which radiosensitivity parameter E0 is assumed to be LET independent and equal to D37 for gamma-rays. For E. coli K-12 wild type, AB1157 (rec+, uvr+), however, it is impossible to interpret the inactivation cross section data by an LET-independent E0-value. In the latter case, as in the case of B. subtilis spore, it is necessary to assume that the radiosensitivity of the target for the core of a heavy ion is higher than that for delta-electrons. As well as Waligorski, Hamm and Katz's dose, the dose around the trajectory of an ion based on Tabata and Ito's energy deposition algorithm for electrons has been used in the course of analysis.
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A comparative study on liquid core formulation on the diameter on the alginate capsules
NASA Astrophysics Data System (ADS)
Ong, Hui-Yen; Lee, Boon-Beng; Radzi, AkmalHadi Ma'; Zakaria, Zarina; Chan, Eng-Seng
2015-08-01
Liquid core capsule has vast application in biotechnology related industries such as pharmaceutical, medical, agriculture and food. Formulation of different types of capsule was important to determine the performance of the capsule. Generally, the liquid core capsule with different formulations generated different size of capsule.Therefore, the aim of this project is to investigate the effect of different liquid core solution formulations on the diameter of capsule. The capsule produced by extruding liquid core solutions into sodium alginate solution. Three types of liquid core solutions (chitosan, xanthan gum, polyethylene glycol (PEG)) were investigated. The results showed that there is significant change in capsule diameter despite in different types of liquid core solution were used and a series of capsule range in diameter of 3.1 mm to 4.5 mm were produced. Alginate capsule with chitosan formulation appeared to be the largest capsule among all.
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Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.
Adams, Stephen R; Yang, Howard C; Savariar, Elamprakash N; Aguilera, Joe; Crisp, Jessica L; Jones, Karra A; Whitney, Michael A; Lippman, Scott M; Cohen, Ezra E W; Tsien, Roger Y; Advani, Sunil J
2016-10-04
Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery.
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Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize
Adams, Stephen R.; Yang, Howard C.; Savariar, Elamprakash N.; Aguilera, Joe; Crisp, Jessica L.; Jones, Karra A.; Whitney, Michael A.; Lippman, Scott M.; Cohen, Ezra E. W.; Tsien, Roger Y.; Advani, Sunil J.
2016-01-01
Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery. PMID:27698471
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Actual questions raised by nanoparticle radiosensitization
NASA Astrophysics Data System (ADS)
Brun, Emilie; Sicard-Roselli, Cécile
2016-11-01
Radiosensitization by metallic nanoparticles (NP) has been explored for more than a decade with promising results in vitro and in cellulo reported in a vast number of publications. Yet, few clinical trials are on-going. This could be related to the lack of selectivity of NP leading to massive quantities to be injected to observe an effect but also to the higher degree of complexity than first thought leading to an absence of consensus probably caused by the lack of standardization in pre-clinical studies. Given the wide panel of NP used, in terms of core nature, size, coating, not to mention of cell lines and irradiation modalities, cross-comparison of data is not a walk in the park. But only a thorough examination could help identifying the key parameters and the possible mechanisms involved. This step is crucial as it should provide guidance for designing the most efficient combination NP/radiation and rationally establishing clinical protocols. In this review, we will combine and confront cellular radiosensitization results with in vitro and numerical experiments in order to give the more recent vision of this complex phenomenon. We decided to address a few hot topics such as the influence of the incident radiation energy, the localization of NP or the so-called ;biological; effect. We will highlight that among the barriers to break down, some are not restricted to the ;nano; community: an incontestable support could be offered by the ;radiation; community in the broadest sense.
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NASA Astrophysics Data System (ADS)
Smirnova, O. A.; Yonezawa, M.
Effects of low dose rate chronic irradiation on radiosensitivity of mammals mice are studied by experimental and modeling methods Own and reference experiments show that priming chronic low-level short-term and long-term exposures to radiation induce respectively elevated radiosensitivity and lowered radiosensitivity radioresistance in mice The manifestation of these radiosensitization and radioprotection effects are respectively increased and decreased mortality of preirradiated specimens after challenge acute irradiation in comparison with those for previously unexposed ones Taking into account that the reason of the animal death in the experiments was the hematopoietic syndrome the biophysical models of the critical body system hematopoiesis are used to simulate the dynamics of the major hematopoietic lines in mice exposed to challenge acute irradiation following the chronic one Juxtaposition of the modeling results obtained and the relevant experimental data shows that the radiosensitization effect of chronic low-level short-term less than 1 month preirradiation on mice is due to increased radiosensitivity of lymphopoietic granulocytopoietic and erythropoietic systems accompanied by increased or close to the normal level radiosensitivity of thrombocytopoietic system which are induced by the above-indicated exposure In turn the radioprotection effect of chronic low-level long-term more than 1 month preirradiation on mice is caused by decreased radiosensitivity radioresistance of the granulocytopoietic system which
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Experimental and Theoretical Investigations on Viscosity of Fe-Ni-C Liquids at High Pressures
NASA Astrophysics Data System (ADS)
Chen, B.; Lai, X.; Wang, J.; Zhu, F.; Liu, J.; Kono, Y.
2016-12-01
Understanding and modeling of Earth's core processes such as geodynamo and heat flow via convection in liquid outer cores hinges on the viscosity of candidate liquid iron alloys under core conditions. Viscosity estimates from various methods of the metallic liquid of the outer core, however, span up to 12 orders of magnitude. Due to experimental challenges, viscosity measurements of iron liquids alloyed with lighter elements are scarce and conducted at conditions far below those expected for the outer core. In this study, we adopt a synergistic approach by integrating experiments at experimentally-achievable conditions with computations up to core conditions. We performed viscosity measurements based on the modified Stokes' floating sphere viscometry method for the Fe-Ni-C liquids at high pressures in a Paris-Edinburgh press at Sector 16 of the Advanced Photon Source, Argonne National Laboratory. Our results show that the addition of 3-5 wt.% carbon to iron-nickel liquids has negligible effect on its viscosity at pressures lower than 5 GPa. The viscosity of the Fe-Ni-C liquids, however, becomes notably higher and increases by a factor of 3 at 5-8 GPa. Similarly, our first-principles molecular dynamics calculations up to Earth's core pressures show a viscosity change in Fe-Ni-C liquids at 5 GPa. The significant change in the viscosity is likely due to a liquid structural transition of the Fe-Ni-C liquids as revealed by our X-ray diffraction measurements and first-principles molecular dynamics calculations. The observed correlation between structure and physical properties of liquids permit stringent benchmark test of the computational liquid models and contribute to a more comprehensive understanding of liquid properties under high pressures. The interplay between experiments and first-principles based modeling is shown to be a practical and effective methodology for studying liquid properties under outer core conditions that are difficult to reach with the current static high-pressure capabilities. The new viscosity data from experiments and computations would provide new insights into the internal dynamics of the outer core.
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RF cavity using liquid dielectric for tuning and cooling
Popovic, Milorad [Warrenville, IL; Johnson, Rolland P [Newport News, VA
2012-04-17
A system for accelerating particles includes an RF cavity that contains a ferrite core and a liquid dielectric. Characteristics of the ferrite core and the liquid dielectric, among other factors, determine the resonant frequency of the RF cavity. The liquid dielectric is circulated to cool the ferrite core during the operation of the system.
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Study on micro-bend light transmission performance of novel liquid-core optical fiber
NASA Astrophysics Data System (ADS)
Ma, Junyan; Zhao, Zhimin; Wang, Kaisheng; Guo, Linfeng
2007-01-01
With the increasing development of material technology and electronic integration technology, optical fiber and its using in smart structure have become hot in the field of material research. And liquid-core optical fiber is a special kind of optical fiber, which is made using liquid material as core and polymer material as optical layer and protective covering, and it has the characteristics of large core diameter, high numerical aperture, large-scope and efficient spectrum transmission and long life for using. So the liquid-core optical fiber is very suitable for spectrum cure, ultraviolet solidification, fluorescence detection, criminal investigation and evidence obtainment, etc, and especially as light transfer element in some new structures for the measurement of some signals, such as concentration, voltage, temperature, light intensity and so on. In this paper, the novel liquid-core optical fiber is self-made, and then through the test of its light transmission performance in free state, the relation between axial micro-bend and light-intensity loss are presented. When the liquid-core optical fiber is micro-bent axially, along with the axial displacement's increase, output power of light is reducing increasingly, and approximately has linear relation to micro-displacement in a range. According to the results liquid-core fiber-optic micro-bend sensor can be designed to measure micro-displacement of the tested objects. Experimental data and analysis provide experimental basis for further application of liquid-core optical fiber.
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Lemieux, Robert P
2007-12-01
This critical review focuses on the induction of polar order in smectic liquid crystal phases by dopants with axially chiral cores, and should be of interest to all practitioners of supramolecular chemistry. The variations in polarization power of these dopants with the core structure of the liquid crystal hosts is a manifestation of molecular recognition that reflects the nanosegregation of aromatic cores from paraffinic side-chains in smectic phases, and the collective effect of core-core interactions that enable the propagation of chiral perturbations.
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Highly Sensitive Liquid Core Temperature Sensor Based on Multimode Interference Effects
Fuentes-Fuentes, Miguel A.; May-Arrioja, Daniel A.; Guzman-Sepulveda, José R.; Torres-Cisneros, Miguel; Sánchez-Mondragón, José J.
2015-01-01
A novel fiber optic temperature sensor based on a liquid-core multimode interference device is demonstrated. The advantage of such structure is that the thermo-optic coefficient (TOC) of the liquid is at least one order of magnitude larger than that of silica and this, combined with the fact that the TOC of silica and the liquid have opposite signs, provides a liquid-core multimode fiber (MMF) highly sensitive to temperature. Since the refractive index of the liquid can be easily modified, this allows us to control the modal properties of the liquid-core MMF at will and the sensor sensitivity can be easily tuned by selecting the refractive index of the liquid in the core of the device. The maximum sensitivity measured in our experiments is 20 nm/°C in the low-temperature regime up to 60 °C. To the best of our knowledge, to date, this is the largest sensitivity reported for fiber-based MMI temperature sensors. PMID:26512664
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Synthesis and radiosensitization properties of hydrogen peroxide and sodium hyaluronate complex
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai
2014-09-03
Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus radiosensitizer agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the radiosensitization properties of radiosensitizer complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for radiosensitizing effect. HepG2 cancer cells are cultured as the mean of test subject. Cancer cell samplesmore » which are targeted and not targeted with these radiosensitizers are irradiated with 2Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with radiosensitizers has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with radiosensitizers prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these radiosensitizers, cancer cells are more sensitive towards radiation.« less
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Synthesis and radiosensitization properties of hydrogen peroxide and sodium hyaluronate complex
NASA Astrophysics Data System (ADS)
Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai; Rahman, Irman Abdul; Ahmad, Ainee Fatimah; Mohamad, Hur Munawar Kabir
2014-09-01
Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus radiosensitizer agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the radiosensitization properties of radiosensitizer complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for radiosensitizing effect. HepG2 cancer cells are cultured as the mean of test subject. Cancer cell samples which are targeted and not targeted with these radiosensitizers are irradiated with 2Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with radiosensitizers has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with radiosensitizers prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these radiosensitizers, cancer cells are more sensitive towards radiation.
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MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1.
Fan, Haoning; Shao, Meng; Huang, Shaohui; Liu, Ying; Liu, Jie; Wang, Zhiyuan; Diao, Jianxin; Liu, Yuanliang; Tong, L I; Fan, Qin
2016-06-01
Curcumin (Cur) exhibits radiosensitization effects to a variety of malignant tumors. The present study investigates the radiosensitizing effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the radiosensitizing effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the radiosensitizing effect in vivo . A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3' UTR of MDR1. The clonogenic assay showed that Cur enhanced the radiosensitivity of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo , resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a radiosensitizing effect on NPC cells in vivo and in vitro ; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote radiosensitivity of NPC cells.
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Makurat, Samanta; Chomicz-Mańka, Lidia; Rak, Janusz
2016-08-18
Although 5-bromo-2'-deoxyuridine (5BrdU) possesses significant radiosensitizing power in vitro, clinical studies do not confirm any advantages of radiotherapy employing 5BrdU. This situation calls for a continuous search for efficient radiosensitizers. Using the proposed mechanism of radiosensitization by 5BrdU, we propose a series of 5-substituted uracils, XYU, that should undergo efficient dissociative electron attachment. The DFT-calculated thermodynamic and kinetic data concerning the XYU degradations induced by electron addition suggests that some of the scrutinized derivatives have much better characteristics than 5BrdU itself. Synthesis of these promising candidates for radiosensitizers, followed by studies of their radiosensitizing properties in DNA context, and ultimately in cancer cells, are further steps to confirm their potential applicability in anticancer treatment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Magnetic suspension using high temperature superconducting cores
NASA Technical Reports Server (NTRS)
Scurlock, R. G.
1992-01-01
The development of YBCO high temperature superconductors, in wire and tape forms, is rapidly approaching the point where the bulk transport current density j vs magnetic field H characteristics with liquid nitrogen cooling will enable its use in model cores. On the other hand, BSCCO high temperature superconductor in wire form has poor j-H characteristics at 77 K today, although with liquid helium or hydrogen cooling, it appears to be superior to NbTi superconductor. Since liquid nitrogen cooling is approx. 100 times cheaper than liquid helium cooling, the use of YBCO is very attractive for use in magnetic suspension. The design is discussed of a model core to accommodate lift and drag loads up to 6000 and 3000 N respectively. A comparison is made between the design performance of a liquid helium cooled NbTi (or BSCCO) superconducting core and a liquid nitrogen cooled YBCO superconducting core.
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Measurement of intact-core length of atomizing liquid jets by image deconvolution
NASA Technical Reports Server (NTRS)
Woodward, Roger; Burch, Robert; Kuo, Kenneth; Cheung, Fan-Bill
1993-01-01
The investigation of liquid jet breakup and spray development is critical to the understanding of combustion phenomena in liquid propellant rocket engines. Much work has been done to characterize low-speed liquid jet breakup and dilute sprays, but atomizing jets and dense sprays have yielded few quantitative measurements due to their high liquid load fractions and hence their optical opacity. Focus was on a characteristic of the primary breakup process of round liquid jets, namely the length of the intact-liquid core. The specific application considered is that of shear-coaxial-type rocket engine injectors in which liquid oxygen is injected through the center post while high velocity gaseous hydrogen is injected through a concentric annulus, providing a shear force to the liquid jet surface. Real-time x ray radiography, capable of imaging through the dense two-phase region surrounding the liquid core, is used to make the measurements. The intact-liquid-core length data were obtained and interpreted using two conceptually different methods to illustrate the effects of chamber pressure, gas-to-liquid momentum ratio, and cavitation.
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Measurement of intact-core length of atomizing liquid jets by image deconvolution
NASA Astrophysics Data System (ADS)
Woodward, Roger; Burch, Robert; Kuo, Kenneth; Cheung, Fan-Bill
1993-11-01
The investigation of liquid jet breakup and spray development is critical to the understanding of combustion phenomena in liquid propellant rocket engines. Much work has been done to characterize low-speed liquid jet breakup and dilute sprays, but atomizing jets and dense sprays have yielded few quantitative measurements due to their high liquid load fractions and hence their optical opacity. Focus was on a characteristic of the primary breakup process of round liquid jets, namely the length of the intact-liquid core. The specific application considered is that of shear-coaxial-type rocket engine injectors in which liquid oxygen is injected through the center post while high velocity gaseous hydrogen is injected through a concentric annulus, providing a shear force to the liquid jet surface. Real-time x ray radiography, capable of imaging through the dense two-phase region surrounding the liquid core, is used to make the measurements. The intact-liquid-core length data were obtained and interpreted using two conceptually different methods to illustrate the effects of chamber pressure, gas-to-liquid momentum ratio, and cavitation.
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Xu, Yonghao; Chen, Xianfeng; Zhu, Yu
2008-03-17
An intensive temperature sensor based on a liquid-core optical fiber has been demonstrated for the measuring the temperature of the environment. The core of fiber is filled with a mixture of toluene and chloroform in order to make the refractive index of the liquid-core and the cladding of the fiber close. The experiment shows that a temperature sensitivity of about 5 dB/K and a tunable temperature range (from 20 o C to 60 o C) can be achieved. Based on the dielectric-clad liquid core fiber model, a simulation was carried out and the calculated results were in good accord with the experimental measurement.
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Daily rhythms of radiosensitivity of animals and several determining causes
NASA Technical Reports Server (NTRS)
Druzhinin, Y. P.; Malyutina, T. S.; Seraya, V. M.; Rodina, G. P.; Vatsek, A.; Rakova, A.
1974-01-01
Daily rhythms of radiosensitivity in rats and mice were determined by survival rates after acute total radiation at the same dosage at different times of the day. Radiosensitivity differed in animals of different species and varieties. Inbred mice exhibited one or two increases in radiosensitivity during the dark, active period of the day. These effects were attributed to periodic changes in the state of stem hematopoietic cells.
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Suzuki, Kenshi; Gerelchuluun, Ariungerel; Hong, Zhengshan; Sun, Lue; Zenkoh, Junko; Moritake, Takashi; Tsuboi, Koji
2013-01-01
Background Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the radiosensitizing effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions. Methods Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or γ-irradiation either alone or in combination under normoxic and hypoxic conditions. Radiosensitizing effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stress–related genes was analyzed by immunoblotting. Results Celecoxib significantly enhanced the radiosensitivity of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and γ-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the radiosensitizing effect of celecoxib was determined to be ER stress loading on GBM cells. Conclusion Celecoxib enhances the radiosensitivity of GBM cells by a mechanism that is different from cyclooxygenase-2 inhibition. Our results indicate that celecoxib may be a promising radiosensitizing drug for clinical use in patients with GBM. PMID:23658321
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Liquid core photonic crystal fiber with low-refractive-index liquids for optofluidic applications.
Park, Jiyoung; Kang, Doo-Eui; Paulson, Bjorn; Nazari, Tavakol; Oh, Kyunghwan
2014-07-14
A defectless hexagonal air-silica photonic crystal fiber (PCF) structure with its central hole selectively filled by a low-refractive-index liquid is numerically analyzed. Despite the fact that the refractive index of the liquid is significantly lower than that of silica, we found an optimal range of waveguide parameters to ensure light guidance through the liquid core in the fundamental mode, maximizing the light-liquid interaction over a desired wavelength range. Using the vectorial finite element method (FEM), we report detailed parametric studies in terms of the effective index, chromatic dispersion, optical loss, and modal intensity distribution of the liquid core PCFs.
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Liquid-filled simplified hollow-core photonic crystal fiber
NASA Astrophysics Data System (ADS)
Liu, Shengnan; Gao, Wei; Li, Hongwei; Dong, Yongkang; Zhang, Hongying
2014-12-01
We report on a novel type of liquid-filled simplified hollow-core photonic crystal fibers (HC-PCFs), and investigate their transmission properties with various filling liquids, including water, ethanol and FC-40. The loss and dispersion characterizations are calculated for different fiber parameters including strut thickness and core diameter. The results show that there are still low-loss windows existing for liquid-filled simplified HC-PCFs, and the low-loss windows and dispersions can be easily tailored by filling different liquids. Such liquid-filled simplified HC-PCFs open up many possibilities for nonlinear fiber optics, optical, biochemical and medical sensing.
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[Synthesis of 1-substituted nitroimidazoles and its evaluation as radiosensitizing agents].
Adams, D R; Martul, R; Alvarez, M V; López Zumel, M C; Espada, M
1991-01-01
The synthesis of various substituted nitroimidazoles with lipophilic and hydrophilic side chains as potential radiosensitizing agents is described. The starting material employed was 4(5)-nitroimidazole, which was alkylated via the sodium salt with various chloro-methylated, substituted alcohols and esters, in order to obtain analogues of misonidazole, metronidazole and desmethylmisonidazole of known radiosensitizing and bactericidal activity. Some final products were assayed for their radiosensitizing properties giving negative results under the testing conditions used.
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Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests
Kriegs, Malte; Kasten-Pisula, Ulla; Riepen, Britta; Hoffer, Konstantin; Struve, Nina; Myllynen, Laura; Braig, Friederike; Binder, Mascha; Rieckmann, Thorsten; Grénman, Reidar; Petersen, Cordula; Dikomey, Ekkehard; Rothkamm, Kai
2016-01-01
The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells. PMID:27281611
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yuan, Xiaopeng; Du, Jie; Hua, Song
Radiotherapy is an essential component of the standard therapy for newly diagnosed glioblastoma. To increase the radiosensitivity of glioma cells is a feasible solution to improve the therapeutic effects. It has been suggested that inhibition of signal transducer and activator of transcription 3 (STAT3) can radiosensitize glioma cells, probably via the activation of mitochondrial apoptotic pathway. In this study, human malignant glioma cells, U251 and A172, were treated with an STAT3 inhibitor, WP1066, or a short hairpin RNA plasmid targeting STAT3 to suppress the activation of STAT3 signaling. The radiosensitizing effects of STAT3 inhibition were confirmed in glioma cells. Intriguingly,more » combination of ionizing radiation exposure and STAT3 inhibition triggered a pronounced increase of autophagy flux. To explore the role of autophagy, glioma cells were treated with 3-methyladenine or siRNA for autophagy-related gene 5, and it was demonstrated that inhibition of autophagy further strengthened the radiosensitizing effects of STAT3 inhibition. Accordingly, more apoptotic cells were induced by the dual inhibition of autophagy and STAT3 signaling. In conclusion, our data revealed a protective role of autophagy in the radiosensitizing effects of STAT3 inhibition, and inhibition of both autophagy and STAT3 might be a potential therapeutic strategy to increase the radiosensitivity of glioma cells. - Highlights: • Inactivation of STAT3 signaling radiosensitizes malignant glioma cells. • STAT3 inhibition triggers a significant increase of autophagy flux induced by ionizing radiation in glioma cells. • Suppression of autophagy further strengthens the radiosensitizing effects of STAT3 inhibition in glioma cells. • Dual inhibition of autophagy and STAT3 induce massive apoptotic cells upon exposure to ionizing radiation.« less
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Primary atomization of liquid jets issuing from rocket engine coaxial injectors
NASA Astrophysics Data System (ADS)
Woodward, Roger D.
1993-01-01
The investigation of liquid jet breakup and spray development is critical to the understanding of combustion phenomena in liquid-propellant rocket engines. Much work has been done to characterize low-speed liquid jet breakup and dilute sprays, but atomizing jets and dense sprays have yielded few quantitative measurements due to their optical opacity. This work focuses on a characteristic of the primary breakup process of round liquid jets, namely the length of the intact liquid core. The specific application considered is that of shear-coaxial type rocket engine injectors. Real-time x-ray radiography, capable of imaging through the dense two-phase region surrounding the liquid core, has been used to make the measurements. Nitrogen and helium were employed as the fuel simulants while an x-ray absorbing potassium iodide aqueous solution was used as the liquid oxygen (LOX) simulant. The intact-liquid-core length data have been obtained and interpreted to illustrate the effects of chamber pressure (gas density), injected-gas and liquid velocities, and cavitation. The results clearly show that the effect of cavitation must be considered at low chamber pressures since it can be the dominant breakup mechanism. A correlation of intact core length in terms of gas-to-liquid density ratio, liquid jet Reynolds number, and Weber number is suggested. The gas-to-liquid density ratio appears to be the key parameter for aerodynamic shear breakup in this study. A small number of hot-fire, LOX/hydrogen tests were also conducted to attempt intact-LOX-core measurements under realistic conditions in a single-coaxial-element rocket engine. The tests were not successful in terms of measuring the intact core, but instantaneous imaging of LOX jets suggests that LOX jet breakup is qualitatively similar to that of cold-flow, propellant-simulant jets. The liquid oxygen jets survived in the hot-fire environment much longer than expected, and LOX was even visualized exiting the chamber nozzle under some conditions. This may be an effect of the single element configuration.
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Chen, Xiaoyan; Zhu, Lin; Zhang, Hang; Wang, Chen; Shao, Chunlin
2017-01-01
Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered. After irradiation with equivalent doses of γ-rays and α-particles, the foci number of histone H3 lysine 9 dimethylation (H3K9me3) and the activity of histone deacetylase (HDAC) in DCs-γ was extensively higher than these in DCs-α and its parent control, indicating that a higher level of heterochromatin was formed in DCs-γ but not in DCs-α. Treatment of cells with SAHA (an inhibitor of HDAC) decreased the level of heterochromatin domains by inhibiting the expressions of H3K9m3 and HP-1a proteins and triggering the expression of acetylated core histone H3 (Ac-H3). When cells were treated with SAHA, the radioresistance phenotype of DCs-γ was eliminated so that the radiosensitivities of DCs-γ, DCs-α and their parent cells approached to same levels. Our current results reveal that γ-rays but not α-particles could induce chromatin remodeling and heterochromatinization which results in the occurrence of radioresistance of DCs, indicating that the combination treatment of irradiation and HDAC inhibitor could serve as a potential cancer therapy strategy, especially for the fraction radiotherapy of low-LET irradiation. PMID:28881774
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Murata, Yasuhiko; Hashimoto, Takuma; Urushihara, Yusuke; Shiga, Soichiro; Takeda, Kazuya; Jingu, Keiichi; Hosoi, Yoshio
2018-01-22
Presence of unperfused regions containing cells under hypoxia and nutrient starvation contributes to radioresistance in solid human tumors. It is well known that hypoxia causes cellular radioresistance, but little is known about the effects of nutrient starvation on radiosensitivity. We have reported that nutrient starvation induced decrease of mTORC1 activity and decrease of radiosensitivity in an SV40-transformed human fibroblast cell line, LM217, and that nutrient starvation induced increase of mTORC1 activity and increase of radiosensitivity in human liver cancer cell lines, HepG2 and HuH6 (Murata et al., BBRC 2015). Knockdown of mTOR using small interfering RNA (siRNA) for mTOR suppressed radiosensitivity under nutrient starvation alone in HepG2 cells, which suggests that mTORC1 pathway regulates radiosensitivity under nutrient starvation alone. In the present study, effects of hypoxia and nutrient starvation on radiosensitivity were investigated using the same cell lines. LM217 and HepG2 cells were used to examine the effects of hypoxia and nutrient starvation on cellular radiosensitivity, mTORC1 pathway including AMPK, ATM, and HIF-1α, which are known as regulators of mTORC1 activity, and glycogen storage, which is induced by HIF-1 and HIF-2 under hypoxia and promotes cell survival. Under hypoxia and nutrient starvation, AMPK activity and ATM expression were increased in LM217 cells and decreased in HepG2 cells compared with AMPK activity under nutrient starvation alone or ATM expression under hypoxia alone. Under hypoxia and nutrient starvation, radiosensitivity was decreased in LM217 cells and increased in HepG2 cells compared with radiosensitivity under hypoxia alone. Under hypoxia and nutrient starvation, knockdown of AMPK decreased ATM activity and increased radiation sensitivity in LM217 cells. In both cell lines, mTORC1 activity was decreased under hypoxia and nutrient starvation. Under hypoxia alone, knockdown of mTOR slightly increased ATM expression but did not affect radiosensitivity in LM217. Under hypoxia and nutrient starvation, HIF-1α expression was suppressed and glycogen storage was reduced. Our data suggest that AMPK regulates ATM expression and partially regulates radiosensitivity under hypoxia and nutrient starvation. The molecular mechanism underlying the induction of ATM expression by AMPK remains to be elucidated. Copyright © 2017. Published by Elsevier Inc.
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Flexible liquid core light guide with focusing and light shaping attachments
Kross, B.J.; Majewski, S.; Zorn, C.J.; Majewski, L.A.
1997-11-04
A liquid light guide system for ultraviolet light is disclosed that has a light shaping arrangement for the emitted light, a stable liquid core and sheath and reliable and effective end closures. 12 figs.
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NASA Astrophysics Data System (ADS)
Zu, Mengjie; Liu, Jun; Tong, Hua; Xu, Ning
2016-08-01
We find that both continuous and discontinuous hexatic-liquid transitions can happen in the melting of two-dimensional solids of soft-core disks. For three typical model systems, Hertzian, harmonic, and Gaussian-core models, we observe the same scenarios. These systems exhibit reentrant crystallization (melting) with a maximum melting temperature Tm happening at a crossover density ρm. The hexatic-liquid transition at a density smaller than ρm is discontinuous. Liquid and hexatic phases coexist in a density interval, which becomes narrower with increasing temperature and tends to vanish approximately at Tm. Above ρm, the transition is continuous, in agreement with the Kosterlitz-Thouless-Halperin-Nelson-Young theory. For these soft-core systems, the nature of the hexatic-liquid transition depends on density (pressure), with the melting at ρm being a plausible transition point from discontinuous to continuous hexatic-liquid transition.
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Radiosensitization of cancer cells by hydroxychalcones.
Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L; Sekhar, Konjeti R
2010-10-15
Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2',5'-dihydroxychalcone (D-601) and 2,2'-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Radiosensitization of Cancer Cells by Hydroxychalcones
Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L.; Sekhar, Konjeti R.
2010-01-01
Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2′,5′-dihydroxychalcone (D-601) and 2,2′-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers. PMID:20826087
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Radiosensitization Effect of STI-571 on Pancreatic Cancer Cells In Vitro
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chung, Hye Won; Wen, Jing; Lim, Jong-Baeck
2009-11-01
Purpose: To examine STI-571-induced radiosensitivity in human pancreatic cancer cells in vitro. Methods and Materials: Three human pancreatic cancer cell lines (Bxpc-3, Capan-1, and MiaPaCa-2) exhibiting different expression levels of c-Kit and platelet-derived growth factor receptor beta (PDGFRbeta) and showing different K-ras mutation types were used. For evaluation of the antitumor activity of STI-571 in combination with radiation, clonogenic survival assays, Western blot analysis, and the annexin V/propidium iodide assay with microscopic evaluation by 4',6-diamidino-2-phenylindole were conducted. Results: Dramatic phosphorylated (p)-c-Kit and p-PDGFRbeta attenuation, a modest dose- and time-dependent growth inhibition, and significant radiosensitization were observed after STI-571 treatment inmore » view of apoptosis, although the levels of growth inhibition and increased radiosensitization were different according to cell lines. The grades of radiosensitivity corresponded to the attenuation levels of p-c-Kit and p-PDGFRbeta by STI-571, particularly to those of p-c-Kit, and the radiosensitivity was partially affected by K-ras mutation in pancreatic cancer cells. Among downstream pathways associated with c-Kit or PDGFRbeta, p-PLCgamma was more closely related to radiosensitivity compared with p-Akt1 or p-extracellular signal-regulated kinase 1. Conclusion: STI-571 enhances radiation response in pancreatic cancer cells. This effect is affected by the attenuation levels of p-c-Kit or p-PDGFRbeta, and K-ras mutation status. Among them, p-c-Kit plays more important roles in the radiosensitivity in pancreatic cancer compared with p-PDGFRbeta or K-ras mutation status.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hannan, M.A.; Smith, B.P.; Sigut, D.
Fibroblast cells derived from a cafe-au-lait spot and normal-appearing skin of a neurofibromatosis (NF-6) patient were studied for radiosensitivity in comparison with two normal cell lines used as controls. No difference in radiosensitivity was observed between the patient's cell lines and the controls using acute gamma-irradiation. However, a markedly increased radiosensitivity of the fibroblasts obtained from the patient's skin of normal appearance was demonstrated after chronic gamma-irradiation. The cells from the cafe-au-lait spot showed intermediate sensitivity to chronic irradiation as compared with the control cell lines and the fibroblasts derived from the normal skin of the patient. These results showedmore » the usefulness of chronic irradiation in detecting increased cellular radiosensitivity which may result from a unique DNA repair defect in an NF patient. We suggest that enhanced genetic changes in radiosensitive NF patients may lead to formation of cafe-au-lait lesions and certain tumors. Such a transformation may be associated with production of radiotolerant cells.« less
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Effects of low-level chronic irradiation on the radiosensitivity of mammals: Modeling studies
NASA Astrophysics Data System (ADS)
Smirnova, O. A.
Mathematical models of the major hematopoietic lines are used to study the modifying effects of low-level chronic preirradiation on radiosensitivity of mammals which resulted in their reduced radiosensitivity (acquired radioresistance) and elevated radiosensitivity (hypersensitivity) to the subsequent radiation exposure. These effects of preirradiation manifest themselves, respectively, in decreased and increased mortality of preirradiated experimental animals (mice) after challenge acute exposure in comparison with that for previously nonirradiated ones. Analysis of the modeling results reveals the biological mechanisms of these radioprotection and radiosensitization effects, and enables one to estimate the ranges of dose rate and duration of chronic preirradiation where these effects are realized. Juxtapositions of the modeling predictions with the relevant experimental data show their qualitative agreement. All this testifies to the importance of accounting the nonlinear effect of low-level chronic irradiation on radiosensitivity of the hematopoiesis system and organism as a whole, when the radiation risk for astronauts on long-term space missions is estimated. The developed models of hematopoiesis can be used, after appropriate identification, as a component of the mathematical tools for radiation risk assessment.
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Differentiation and radiosensitivity of hemopoietic stem cells of mice during hypokinesia
NASA Technical Reports Server (NTRS)
Shvets, V. N.
1980-01-01
The potential for differentiation and radiosensitivity of the stem hemopoietic cells (KOE) under conditions of initial and later hypokinesia is examined. It is established that in the initial period of hypokinesia (3 days) when a stress reaction prevails, changes occur in the erythroid differentiation and radiosensitivity of KOE. This effect is associated with redistribution of T-lymphocytes that increase in number in the bone marrow of mice during hypokinesia. At later periods of hypokinesia (30 days) when changes in the organism are related to hypokinesia proper, differentiation and radiosensitivity of KOE were normalized.
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Fiber optic refractive index monitor
Weiss, Jonathan David
2002-01-01
A sensor for measuring the change in refractive index of a liquid uses the lowest critical angle of a normal fiber optic to achieve sensitivity when the index of the liquid is significantly less than the index of the fiber core. Another embodiment uses a liquid filled core to ensure that its index is approximately the same as the liquid being measured.
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Liquid molded hollow cell core composite articles
NASA Technical Reports Server (NTRS)
Bernetich, Karl R. (Inventor)
2005-01-01
A hollow core composite assembly 10 is provided, including a hollow core base 12 having at least one open core surface 14, a bondable solid film 22 applied to the open core surface 14, at least one dry face ply 30 laid up dry and placed on top of the solid film 22, and a liquid resin 32 applied to the at least one dry face ply 30 and then cured.
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Visual detection of gas shows from coal core and cuttings using liquid leak detector
Barker, C.E.
2006-01-01
Portions of core or cutting samples that have active gas shows can be identified by applying a liquid leak detector to the core surface. Although these gas shows can be caused by manmade changes to the coals' internal structure and surface of the core during the coring process, in many cases, the marked gas shows overlie changes in maceral composition, subtle fractures or coal, coal structure and so forth that seemingly are places where natural primary permeability is higher and gas shows would be favored. Given the limited time available for core description before a core is closed in a canister, using the liquid leak detector method to mark gas shows enhances core description by providing a photographic record of places of apparently increased gas flow likely related to enhanced coal permeability that cannot be easily detected otherwise.
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POWER GENERATION FROM LIQUID METAL NUCLEAR FUEL
Dwyer, O.E.
1958-12-23
A nuclear reactor system is described wherein the reactor is the type using a liquid metal fuel, such as a dispersion of fissile material in bismuth. The reactor is designed ln the form of a closed loop having a core sectlon and heat exchanger sections. The liquid fuel is clrculated through the loop undergoing flssion in the core section to produce heat energy and transferrlng this heat energy to secondary fluids in the heat exchanger sections. The fission in the core may be produced by a separate neutron source or by a selfsustained chain reaction of the liquid fuel present in the core section. Additional auxiliary heat exchangers are used in the system to convert water into steam which drives a turbine.
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Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells.
Cheng, Huawen
2016-09-20
BACKGROUND Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. MATERIAL AND METHODS CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. RESULTS CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. CONCLUSIONS These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Werner, Michael E.; Cummings, Natalie D.; Sethi, Manish
2013-07-01
Purpose: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease. Methods and Materials: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated inmore » vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration. Results: Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of −8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.« less
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Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hirai, Takahisa; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo; Saito, Soichiro
The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in Nationalmore » Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response. - Highlights: • Effective radiosensitizers for particle radiation therapy have not been reported. • PARP inhibitor treatment radiosensitized after proton beam irradiation. • The sensitization at Bragg peak was greater than that at entrance region. • DSB induction and G2/M arrest is involved in the sensitization mechanism.« less
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Schenewerk, William E.; Glasgow, Lyle E.
1983-01-01
A liquid metal cooled fast breeder reactor provided with an emergency core cooling system includes a reactor vessel which contains a reactor core comprising an array of fuel assemblies and a plurality of blanket assemblies. The reactor core is immersed in a pool of liquid metal coolant. The reactor also includes a primary coolant system comprising a pump and conduits for circulating liquid metal coolant to the reactor core and through the fuel and blanket assemblies of the core. A converging-diverging venturi nozzle with an intermediate throat section is provided in between the assemblies and the pump. The intermediate throat section of the nozzle is provided with at least one opening which is in fluid communication with the pool of liquid sodium. In normal operation, coolant flows from the pump through the nozzle to the assemblies with very little fluid flowing through the opening in the throat. However, when the pump is not running, residual heat in the core causes fluid from the pool to flow through the opening in the throat of the nozzle and outwardly through the nozzle to the assemblies, thus providing a means of removing decay heat.
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Diffusive Transport and Structural Properties of Liquid Iron Alloys at High Pressure
NASA Astrophysics Data System (ADS)
Posner, E.; Rubie, D. C.; Steinle-Neumann, G.; Frost, D. J.
2017-12-01
Diffusive transport properties of liquid iron alloys at high pressures (P) and temperatures (T) place important kinetic constraints on processes related to the origin and evolution of planetary cores. Earth's core composition is largely controlled by the extent of chemical equilibration achieved between liquid metal bodies and a silicate magma ocean during core formation, which can be estimated using chemical diffusion data. In order to estimate the time and length scales of metal-silicate chemical equilibration, we have measured chemical diffusion rates of Si, O and Cr in liquid iron over the P-T range of 1-18 GPa and 1873-2643 K using a multi-anvil apparatus. We have also performed first-principles molecular dynamic simulations of comparable binary liquid compositions, in addition to pure liquid Fe, over a much wider P-T range (1 bar-330 GPa, 2200-5500 K) in order to both validate the simulation results with experimental data at conditions accessible in the laboratory and to extend our dataset to conditions of the Earth's core. Over the entire P-T range studied using both methods, diffusion coefficients are described consistently and well using an exponential function of the homologous temperature relation. Si, Cr and Fe diffusivities of approximately 5 × 10-9 m2 s-1 are constant along the melting curve from ambient to core pressures, while oxygen diffusion is 2-3 times faster. Our results indicate that in order for the composition of the Earth's core to represent chemical equilibrium, impactor cores must have broken up into liquid droplet sizes no larger than a few tens of cm. Structural properties, analyzed using partial radial distribution functions from the molecular dynamics simulations, reveal a pressure-induced structural change in liquid Fe0.96O0.04 at densities of 8 g cm-3, in agreement with previous experimental studies. For densities above 8 g cm-3, the liquid is essentially close packed with a local CsCl-like (B2) packing of Fe around O under conditions of the Earth's core.
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In situ TEM and analytical STEM studies of ZnO nanotubes with Sn cores and Sn nanodrops
NASA Astrophysics Data System (ADS)
Ortega, Y.; Jäger, W.; Piqueras, J.; Häussler, D.; Fernández, P.
2013-10-01
ZnO nanorods with Sn core regions grown by a thermal evaporation-deposition method from a mixture of SnO2 and ZnS powders as precursors, are used to study the behaviour of liquid metal in the nanotubes' core regions and the formation of liquid metal nanodrops at the tube ends by in situ TEM experiments. The compositions of the core materials and of the nanodrops were assessed by employing HAADF-STEM imaging and spatially resolved EDXS measurements. By applying variable thermal load through changing the electron-beam flux of the electron microscope, melting of the metallic core can be induced and the behaviour of the liquid metal of the nanorods can be monitored locally. Within the nanorod core, melting and reversible thermal expansion and contraction of Sn core material is reproducibly observed. For nanotubes with core material near-tip regions, a nanodrop emerges from the tip upon melting the core material, followed by reabsorption of the melt into the core and re-solidification upon decreasing the heat load, being reminiscent of a ‘soldering nanorod’. The radius of the liquid nanodrop can reach a few tens of nanometres, containing a total volume of 10-20 up to 10-18 l of liquid Sn. In situ TEM confirms that the radius of the nanodrop can be controlled via the thermal load: it increases with increasing temperature and decreases with decreasing temperature. In addition, some phenomena related to structure modifications during extended electron-beam exposure are also described.
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NASA Astrophysics Data System (ADS)
Lou, Weimin; Chen, Debao; Shen, Changyu; Lu, Yanfang; Liu, Huanan; Wei, Jian
2016-01-01
A simple liquid level sensor using a small piece of hydrofluoric acid (HF) etched polarization maintaining fiber (PMF), with SMF-PMF-SMF fiber structure based on Mach- Zehnder interference (MZI) mechanism is proposed. The core-offset fusion splicing method induced cladding modes interfere with the core mode. Moreover, the changing liquid level would influence the optical path difference of the MZI since the effective refractive indices of the air and the liquid is different. Both the variations of the wavelength shifts and power intensity attenuation corresponding to the liquid level can be obtained with a sensitivity of 0.4956nm/mm and 0.2204dB/mm, respectively.
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Change in radiosensitivity of rats during hypokinetic stress
NASA Technical Reports Server (NTRS)
Chernov, I. P.
1980-01-01
The laws governing stress modification of radiation sickness in relation to hypokinetic stress were investigated. It was found that gamma irradiation (800 rad) of rats on the third day of exposure to hypokinesia increased the radiosensitivity of the animals which was determined by the survival rate and the dynamics of body weight and the weight of some internal organs. The same radiation dose was given on the 20th day of hypokinesia and on the third day of recovery from the 20 day hypokinesia decreased the radiosensitivity of rats. It is concluded that the variations in the radiosensitivity observed may be due to a stress effect of hypokinesia.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Maruyama, Y.; Magura, C.; Feola, J.
1977-07-01
Ten days after total-body irradiation with 550 rads of /sup 60/Co, spleen colonies were observed in adult C57BL mice. A change in radiosensitivity induced by Corynebacterium parvum, as measured by increased numbers of colony-forming units that survived the 550 rads, began shortly after C. parvum stimulation and extended for at least 7 days before irradiation. C. parvum given 4-24 hours before, followed by high specific activity (/sup 3/H)thymidine (HSATT) 1 hour before total-body irradiation greatly reduced survival of the stem cells that formed spleen colonies (CFU/sub s/) and CFU/sub s/ radiosensitivity to control levels. The HSATT sensitivity by ''suicide'' assaymore » in vivo and the time-response change in radiosensitivity corresponded with the decrease in radiosensitivity, which showed that CFU/sub s/ were stimulated by C. parvum administration and entered the S-phase shortly after stimulation. The data indicated a resting population close to the S-phase. After stimulation, this population entered S-phase. Syngeneic mouse lymphoma cells injected iv 24 hours earlier did not elicit any effect as a stimulus to CFU/sub s/ radiosensitivity change.« less
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The impact of different dose response parameters on biologically optimized IMRT in breast cancer
NASA Astrophysics Data System (ADS)
Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.
2008-05-01
The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.
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Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?
De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H
2008-01-01
The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients. PMID:18414410
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Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?
De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H
2008-05-20
The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G(2) scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (
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Lesueur, Paul; Chevalier, François; Austry, Jean-Baptiste; Waissi, Waisse; Burckel, Hélène; Noël, Georges; Habrand, Jean-Louis; Saintigny, Yannick; Joly, Florence
2017-09-15
Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, G2/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their radio-sensitization effect. Here, after highlighting mechanisms of PARP inhibitors radiosensitization we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor radiosensitizing effect. Enhancement ratio, when available, was systematically reported. Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any radiosensitizing effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data. PARP inhibitors are promising radiosensitizers, but need more clinical investigation. The next ten years will be determining for judging their real potential.
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Warenius, H M; Jones, M; Gorman, T; McLeish, R; Seabra, L; Barraclough, R; Rudland, P
2000-01-01
The tumour suppressor gene, p53, and genes coding for positive signal transduction factors can influence transit through cell-cycle checkpoints and modulate radiosensitivity. Here we examine the effects of RAF1 protein on the rate of exit from a G2/M block induced by γ-irradiation in relation to intrinsic cellular radiosensitivity in human cell lines expressing wild-type p53 (wtp53) protein as compared to mutant p53 (mutp53) protein. Cell lines which expressed mutp53 protein were all relatively radioresistant and exhibited no relationship between RAF1 protein and cellular radiosensitivity. Cell lines expressing wtp53 protein, however, showed a strong relationship between RAF1 protein levels and the radiosensitivity parameter SF2. In addition, when post-irradiation perturbation of G2/M transit was compared using the parameter T50 (time after the peak of G2/M delay at which 50% of the cells had exited from a block induced by 2 Gy of irradiation), RAF1 was related to T50 in wtp53, but not mutp53, cell lines. Cell lines which expressed wtp53 protein and high levels of RAF1 had shorter T50s and were also more radiosensitive. These results suggest a cooperative role for wtp53 and RAF1 protein in determining cellular radiosensitivity in human cells, which involves control of the G2/M checkpoint. © 2000 Cancer Research Campaign PMID:10993658
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Liquid level, void fraction, and superheated steam sensor for nuclear-reactor cores. [PWR; BWR
Tokarz, R.D.
1981-10-27
This disclosure relates to an apparatus for monitoring the presence of coolant in liquid or mixed liquid and vapor, and superheated gaseous phases at one or more locations within an operating nuclear reactor core, such as pressurized water reactor or a boiling water reactor.
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NASA Astrophysics Data System (ADS)
Takeda, Takeshi; Maruyama, Yu; Watanabe, Tadashi; Nakamura, Hideo
Experiments simulating PWR intermediate-break loss-of-coolant accidents (IBLOCAs) with 17% break at hot leg or cold leg were conducted in OECD/NEA ROSA-2 Project using the Large Scale Test Facility (LSTF). In the hot leg IBLOCA test, core uncovery started simultaneously with liquid level drop in crossover leg downflow-side before loop seal clearing (LSC) induced by steam condensation on accumulator coolant injected into cold leg. Water remained on upper core plate in upper plenum due to counter-current flow limiting (CCFL) because of significant upward steam flow from the core. In the cold leg IBLOCA test, core dryout took place due to rapid liquid level drop in the core before LSC. Liquid was accumulated in upper plenum, steam generator (SG) U-tube upflow-side and SG inlet plenum before the LSC due to CCFL by high velocity vapor flow, causing enhanced decrease in the core liquid level. The RELAP5/MOD3.2.1.2 post-test analyses of the two LSTF experiments were performed employing critical flow model in the code with a discharge coefficient of 1.0. In the hot leg IBLOCA case, cladding surface temperature of simulated fuel rods was underpredicted due to overprediction of core liquid level after the core uncovery. In the cold leg IBLOCA case, the cladding surface temperature was underpredicted too due to later core uncovery than in the experiment. These may suggest that the code has remaining problems in proper prediction of primary coolant distribution.
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Physical Properties of Liquid Fe-S Alloys at High Pressure
NASA Astrophysics Data System (ADS)
Antonangeli, D.; Morard, G.; Marret, A.; Prescher, C.; Boulard, E.; Mezouar, M.; Rivoldini, A.
2016-12-01
Sulfur is classically considered the dominant light element alloyed to iron in the core of small telluric planets such as Mercury and Mars. The expected pressure (P) and temperature (T) conditions are: P between 6 and 40 GPa and T between 1300 and 2300 K for Mercury's core and P between 24 and 42 GPa and T between 1800 and 2600 K for Mars'core. The presence of an internally generated magnetic field and the amplitude of its 88d libration support the liquid nature of a portion of Merury's core, and various independent lines of evident suggest that Mars's core has been liquid throughout its history. However, as only few experiments, mostly based on sink/float methods studied liquid Fe-S alloys, little is known about the physical properties at these P-T conditions, greatly limiting our capability to produce accurate planetary models. Here we present results of in-situ x-ray diffraction experiments on Fe-S liquids compressed in laser heated diamond anvil cell and of ex-situ electron microcopy analysis of the recovered samples. Our data allowed us to determine the evolution of the eutectic composition with pressure and to establish the eutectic melting curve up to 50 GPa. The x-ray diffuse signal from the liquid is analyzed to derive the density and compressibility of the Fe-S liquid alloys as a function of the S content.
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Armor systems including coated core materials
Chu, Henry S [Idaho Falls, ID; Lillo, Thomas M [Idaho Falls, ID; McHugh, Kevin M [Idaho Falls, ID
2012-07-31
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
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Armor systems including coated core materials
Chu, Henry S; Lillo, Thomas M; McHugh, Kevin M
2013-10-08
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
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Applications of liquid state physics to the earth's core
NASA Technical Reports Server (NTRS)
Stevenson, D. J.
1980-01-01
New results derived for application to the earth's outer core using the modern theory of liquids and the hard-sphere model of liquid structure are presented. An expression derived in terms of the incompressibility and pressure is valid for a high-pressure liquid near its melting point, provided that the pressure is derived from a strongly repulsive pair potential; a relation derived between the melting point and density leads to a melting curve law of essentially the same form as Lindemann's law. Finally, it is shown that the 'core paradox' of Higgins and Kennedy (1971) can occur only if the Gruneisen parameter is smaller than 2/3, and this constant is larger than this value in any liquid for which the pair potential is strongly repulsive.
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NASA Astrophysics Data System (ADS)
Jing, Z.; Chantel, J.; Yu, T.; Sakamaki, T.; Wang, Y.
2015-12-01
Liquid iron is likely the dominant constituent in the cores of terrestrial planets and icy satellites such as Earth, Mars, Mercury, the Moon, Ganymede, and Io. Suggested by geophysical and geochemical observations, light elements such as S, C, Si, etc., are likely present in planetary cores. These light elements can significantly reduce the density and melting temperature of the Fe cores, and hence their abundances are crucial to our understanding of the structure and thermal history of planetary cores, as well as the generation of intrinsic magnetic fields. Knowledge on the density of Fe-light element alloying liquids at high pressures is critical to place constraints on the composition of planetary cores. However, density data on liquid Fe-light element alloys at core pressures are very limited in pressure and composition and are sometimes controversial. In this study, we extend the density dataset for Fe-rich liquids by measuring the density of Fe, Fe-10wt%S, Fe-20wt%S, Fe-27wt%S, and FeS liquids using the X-ray absorption technique in a DIA-type multianvil apparatus up to 7 GPa and 2173 K. An ion chamber (1D-detector) and a CCD camera (2D-detector) were used to measure intensities of transmitted monochromatic X-rays through molten samples, with the photon energy optimized at 40 keV. The densities were then determined from the Beer-Lambert law using the mass absorption coefficients, calibrated by solid standards using X-ray diffraction. At each pressure, density measurements were conducted at a range of temperatures above the liquidus of the samples, enabling the determination of thermal expansion. Combined with our previous results on the sound velocity of Fe and Fe-S liquids at high pressures (Jing et al., 2014, Earth Planet. Sci. Lett. 396, 78-87), these data provide tight constraints on the equation of state and thermodynamic properties such as the adiabatic temperature gradient for Fe-S liquids. We will discuss these results with implications to planetary cores.
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Liquid-filled hollow core microstructured polymer optical fiber.
Cox, F M; Argyros, A; Large, M C J
2006-05-01
Guidance in a liquid core is possible with microstructured optical fibers, opening up many possibilities for chemical and biochemical fiber-optic sensing. In this work we demonstrate how the bandgaps of a hollow core microstructured polymer optical fiber scale with the refractive index of liquid introduced into the holes of the microstructure. Such a fiber is then filled with an aqueous solution of (-)-fructose, and the resulting optical rotation measured. Hence, we show that hollow core microstructured polymer optical fibers can be used for sensing, whilst also fabricating a chiral optical fiber based on material chirality, which has many applications in its own right.
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Flexible, liquid core light guide with focusing and light shaping attachments
Wojcik, Randolph Frank; Majewski, Stanislaw; Zorn, Carl John; Kross, Brian
1999-01-01
A liquid light guide system for ultraviolet light is disclosed that has a light shaping arrangement for the emitted light, a stable liquid core and sheath and reliable and effective end closures. The end closures include a metal crimping arrangement that utilizes two layers of deformable materials to prevent cracking of endplugs.
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2015-05-01
liquid jet core; elliptical EPL is what would be expected from a cylinder of liquid and has previously been observed in diesel injector studies [22...and liquid rocket engines) shear coaxial jets have been stud- ied for over sixty years and have become a canonical problem for the study of rocket...research has been done using a single phase (either gas-gas or liquid - liquid mixing). A brief review of single-phase coaxial jet research can be
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Shvets, V.N.
Studies were made of the direction of differentiation and radiosensitivity of CFU (colony-forming units) of bone marrow and spleen for 1 month after single injection of 5 mg hydrocortisone (HC) per mouse. It was found that there was a sharp change in direction of differentiation of CFU from different sources. Bone marrow CFU enhanced erythropoiesis and CFU of the spleen enhanced myelopoiesis, which is not inherent in the same CFU of normal mice. Determination of radiosensitivity of CFU from different sources according to the spleen colony test failed to demonstrate any differences in value of D/sub 0/ and extrapolation number,more » whereas substantial changes in radiosensitivity were demonstrated in the bone marrow colony test. Radiosensitivity of marrow CFU diminished while that of the spleen increased, as compared to the control. It is assumed that these phenomena are due to redistribution of T lymphocytes in response to HC.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nauman, A F
1979-01-01
The report presents a compilation of available data on the sensitivity of plants to ionizing radiation, and provides basic information on methods of determining such sensitivities, or of estimating radiosensitivities by calcuation of the nuclear factors upon which they depend. The scope of the data presented here is necessarily limited to the most generally useful radiobiological end points and to the most commonly-used types of radiation. Many of the factors which influence radiosensitivity, particularly nuclear factors, will be discussed. Emphasis will be upon whole-plant studies done at Brookhaven National Laboratory by A.H. Sparrow and his associates, since these studies aremore » the source of most of the available radiosensitivity data and of all the sensitivity predictions listed here. Data presented here include summaries of experimentally-determined radiosensitivities at various end points for both herbaceous and woody higher plants, and for a few species of ferns and lower plants. The algae and fungi have not been considered here due to space limitations.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Guo, Pin; Lan, Jin; Ge, Jianwei
Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3′UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer ofmore » GBM. - Highlights: ●miR-26a directly target ATM in GBM cells. ●miR-26a enhances the radiosensitivity of GBM cells. ●miR-26a could reduce the DNA repair capacity of GBM cells.« less
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Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines
Ban, Sadayuki; Michikawa, Yuichi; Ishikawa, Ken-ichi; Sagara, Masashi; Watanabe, Koji; Shimada, Yutaka; Inazawa, Johji; Imai, Takashi
2005-01-01
The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy. PMID:16045545
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A model for osmium isotopic evolution of metallic solids at the core-mantle boundary
NASA Astrophysics Data System (ADS)
Humayun, Munir
2011-03-01
Some plumes are thought to originate at the core-mantle boundary, but geochemical evidence of core-mantle interaction is limited to Os isotopes in samples from Hawaii, Gorgona (89 Ma), and Kostomuksha (2.7 Ga). The Os isotopes have been explained by physical entrainment of Earth's liquid outer core into mantle plumes. This model has come into conflict with geophysical estimates of the timing of core formation, high-pressure experimental determinations of the solid metal-liquid metal partition coefficients (D), and the absence of expected 182W anomalies. A new model is proposed where metallic liquid from the outer core is partially trapped in a compacting cumulate pile of Fe-rich nonmetallic precipitates (FeO, FeS, Fe3Si, etc.) at the top of the core and undergoes fractional crystallization precipitating solid metal grains, followed by expulsion of the residual metallic liquid back to the outer core. The Os isotopic composition of the solids and liquids in the cumulate pile is modeled as a function of the residual liquid remaining and the emplacement age using 1 bar D values, with variable amounts of oxygen (0-10 wt %) as the light element. The precipitated solids evolve Os isotope compositions that match the trends for Hawaii (at an emplacement age of 3.5-4.5 Ga; 5%-10% oxygen) and Gorgona (emplacement age < 1.5 Ga; 0%-5% oxygen). The Fe-rich matrix of the cumulate pile dilutes the precipitated solid metal decoupling the Fe/Mn ratio from Os and W isotopes. The advantages to using precipitated solid metal as the Os host include a lower platinum group element and Ni content to the mantle source region relative to excess iron, miniscule anomalies in 182W (<0.1 ɛ), and no effects for Pb isotopes, etc. A gradual thermomechanical erosion of the cumulate pile results in incorporation of this material into the base of the mantle, where mantle plumes subsequently entrain it. Fractional crystallization of metallic liquids within the CMB provides a consistent explanation of both Os isotope correlations, Os-W isotope systematics, and Fe/Mn evidence for core-mantle interaction over the entire Hawaiian source.
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Metalloporphyrins and their uses as radiosensitizers for radiation therapy
Miura, Michiko; Slatkin, Daniel N.
2004-07-06
The present invention covers radiosensitizers containing as an active ingredient halogenated derivatives of boronated porphyrins containing multiple carborane cages having the structure ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron--capture therapy and photodynamic therapy. The present invention also covers methods for using these radiosensitizers in tumor imaging and cancer treatment.
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Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui
2017-05-10
This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.
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Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui
2017-01-01
This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function. PMID:28489060
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Chen, Guang-Zong; Dai, Wang-Shu; Zhu, Hong-Cheng; Song, Hong-Mei; Yang, Xi; Wang, Yuan-Dong; Min, Hua; Lu, Qian; Liu, Shu; Sun, Xin-Chen; Zeng, Xiao-Ning
2017-01-01
As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer. PMID:28529610
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Mousavi, Mehdi; Nedaei, Hassan Ali; Khoei, Samideh; Eynali, Samira; Khoshgard, Karim; Robatjazi, Mostafa; Iraji Rad, Rasoul
2017-02-01
Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of radiosensitization was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams. It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 μM. Pegylated-GNP are taken up by B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV electrons. The radiosensitization effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.
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NASA Astrophysics Data System (ADS)
Ramalho, Teodorico C.; França, Tanos C. C.; Cortopassi, Wilian A.; Gonçalves, Arlan S.; da Silva, Alan W. S.; da Cunha, Elaine F. F.
2011-04-01
In spite of recent progress, cancer is still one of the most serious health problems of mankind. Recently, it has been discovered that tumor hypoxia can be exploited for selective anticancer treatment using radiosensitizers that are activated only under hypoxic conditions. The most commonly used radiosensitizers are the 5-nitroimidazole derivatives. The toxicity of bioreductive anticancer drugs, such as radiosensitizers is associated to their interaction with DNA. In this work, we have investigated the interaction between the model radiosensitizers metronizole, nimorazole and secnidazole with salmon DNA in order to get insights on the drug-macromolecule interactions. To this end, we have employed NMR techniques (PFG NMR spectra and spin-lattice relaxation rates) in combination with theoretical tools, such as docking calculations and MD simulations. Initially, results show that the δ values are not the most appropriated NMR parameters to map the interaction topology of drug-macromolecule complexes. Furthermore our data indicate that radiosensitizers, in the inactive form, interact considerably with DNA, significantly increasing its toxicity. In fact, we obtained a good agreement between that technique and docking and MD simulations. This suggests that improvements in the structures of these molecules in order to achieve new and more selective bioreductive anticancer drugs are still necessary.
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Radiation biology and oncology in the genomic era.
Kerns, Sarah L; Chuang, Kuang-Hsiang; Hall, William; Werner, Zachary; Chen, Yuhchyau; Ostrer, Harry; West, Catharine; Rosenstein, Barry
2018-06-14
Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects. Current thinking is that some will be tissue specific, and future tests will be tailored to the normal tissues at risk. The relationship between normal and tumor cell radiosensitivity is poorly understood. Data are emerging suggesting interplay between germline genetic variation and epigenetic modification with growing evidence that changes in DNA methylation regulate the radiosensitivity of cancer cells and histone acetyltransferase inhibitors have radiosensitizing effects. Changes in histone methylation can also impair DNA damage response signaling and alter radiosensitivity. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics. To address challenges in harmonizing data from multiple cohorts, the consortium established the REQUITE project to collect standardized data and genotyping for ~5,000 patients. The collection of detailed dosimetric data is important to produce validated multivariable models. Continued efforts will identify new genes that impact on radiosensitivity to generate new knowledge on toxicity pathogenesis and tests to incorporate into the clinical decision-making process.
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Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery.
Buckel, Lisa; Savariar, Elamprakash N; Crisp, Jessica L; Jones, Karra A; Hicks, Angel M; Scanderbeg, Daniel J; Nguyen, Quyen T; Sicklick, Jason K; Lowy, Andrew M; Tsien, Roger Y; Advani, Sunil J
2015-04-01
Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor-targeting technologies allows for developing potent radiosensitizing drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent radiosensitizer and be selectively delivered to tumors using an activatable cell-penetrating peptide targeting matrix metalloproteinases and RGD-binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to radiosensitize both established cancer cells and a low-passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule- and dose-dependent manner, correlating with mitotic arrest. Radiosensitization was evidenced by decreased clonogenic survival and increased DNA double-strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with nontargeted free MMAE or tumor-targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent radiosensitizer. Importantly, MMAE radiosensitization can be localized to tumors by targeted activatable cell-penetrating peptides. ©2015 American Association for Cancer Research.
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Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery
Crisp, Jessica L.; Jones, Karra A.; Hicks, Angel M.; Scanderbeg, Daniel J.; Nguyen, Quyen T.; Sicklick, Jason K.; Lowy, Andrew M.; Tsien, Roger Y.; Advani, Sunil J.
2015-01-01
Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor targeting technologies allows for developing potent radiosensitizing drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent radiosensitizer and be selectively delivered to tumors using an activatable cell penetrating peptide targeting matrix metalloproteinases and RGD binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to radiosensitize both established cancer cells and a low passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule and dose dependent manner correlating with mitotic arrest. Radiosensitization was evidenced by decreased clonogenic survival and increased DNA double strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with non-targeted free MMAE or tumor targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent radiosensitizer. Importantly, MMAE radiosensitization can be localized to tumors by targeted activatable cell penetrating peptides. PMID:25681274
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Morrison, Rachel A; Rybak-Smith, Malgorzata J; Thompson, James M; Thiebaut, Bénédicte; Hill, Mark A; Townley, Helen E
2017-01-01
The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania radiosensitizing nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal radiosensitizing embolic particle for cancer treatment. We have previously shown that radiosensitizing NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as radiosensitizers was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro radiosensitization experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.2%). It was shown that the radiosensitizing NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be radiosensitizing. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors. PMID:28572729
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Morrison, Rachel A; Rybak-Smith, Malgorzata J; Thompson, James M; Thiebaut, Bénédicte; Hill, Mark A; Townley, Helen E
2017-01-01
The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania radiosensitizing nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal radiosensitizing embolic particle for cancer treatment. We have previously shown that radiosensitizing NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as radiosensitizers was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro radiosensitization experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.2%). It was shown that the radiosensitizing NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be radiosensitizing. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors.
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Jayakumar, Sundarraj; Bhilwade, Hari N; Pandey, Badri N; Sandur, Santosh K; Chaubey, Ramesh C
2012-10-09
The assessment of tumor radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. Therefore, the degree of correlation between radiation-induced DNA damage, as measured by the alkaline and the neutral comet assays, and the clonogenic survival of different human tumor cells was studied. Further, tumor radiosensitivity was compared with the expression of genes associated with the cellular response to radiation damage. Five different human tumor cell lines were chosen and the radiosensitivity of these cells was established by clonogenic assay. Alkaline and neutral comet assays were performed in γ-irradiated cells (2-8Gy; either acute or fractionated). Quantitative PCR was performed to evaluate the expression of DNA damage response genes in control and irradiated cells. The relative radiosensitivity of the cell lines assessed by the extent of DNA damage (neutral comet assay) immediately after irradiation (4Gy or 6Gy) was in agreement with radiosensitivity pattern obtained by the clonogenic assay. The survival fraction of irradiated cells showed a better correlation with the magnitude of DNA damage measured by the neutral comet assay (r=-0.9; P<0.05; 6Gy) than evaluated by alkaline comet assay (r=-0.73; P<0.05; 6Gy). Further, a significant correlation between the clonogenic survival and DNA damage was observed in cells exposed to fractionated doses of radiation. Of 15 genes investigated in the gene expression study, HSP70, KU80 and RAD51 all showed significant positive correlations (r=0.9; P<0.05) with tumor radiosensitivity. Our study clearly demonstrated that the neutral comet assay was better than alkaline comet assay for assessment of radiosensitivities of tumor cells after acute or fractionated doses of irradiation. © 2012 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.
2008-01-01
Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by {gamma}H{sub 2}AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observedmore » radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual {gamma}H2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2.« less
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Ferrofluid-based Stretchable Magnetic Core Inductors
NASA Astrophysics Data System (ADS)
Lazarus, N.; Meyer, C. D.
2015-12-01
Magnetic materials are commonly used in inductor and transformer cores to increase inductance density. The emerging field of stretchable electronics poses a new challenge since typical magnetic cores are bulky, rigid and often brittle. This paper presents, for the first time, stretchable inductors incorporating ferrofluid as a liquid magnetic core. Ferrofluids, suspensions of nanoscale magnetic particles in a carrier liquid, provide enhanced magnetic permeability without changing the mechanical properties of the surrounding elastomer. The inductor tested in this work consisted of a liquid metal solenoid wrapped around a ferrofluid core in separate channels. The low frequency inductance was found to increase from 255 nH before fill to 390 nH after fill with ferrofluid, an increase of 52%. The inductor was also shown to survive uniaxial strains of up to 100%.
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NASA Astrophysics Data System (ADS)
Ozawa, Haruka; Hirose, Kei; Yonemitsu, Kyoko; Ohishi, Yasuo
2016-12-01
We carried out melting experiments on Fe-Si alloys to 127 GPa in a laser-heated diamond-anvil cell (DAC). On the basis of textural and chemical characterizations of samples recovered from a DAC, a change in eutectic liquid composition in the Fe-FeSi binary system was examined with increasing pressure. The chemical compositions of coexisting liquid and solid phases were quantitatively determined with field-emission-type electron microprobes. The results demonstrate that silicon content in the eutectic liquid decreases with increasing pressure to less than 1.5 ± 0.1 wt.% Si at 127 GPa. If silicon is a single light element in the core, 4.5 to 12 wt.% Si is required in the outer core in order to account for its density deficit from pure iron. However, such a liquid core, whose composition is on the Si-rich side of the eutectic point, crystallizes less dense solid, CsCl (B2)-type phase at the inner core boundary (ICB). Our data also show that the difference in silicon concentration between coexisting solid and liquid is too small to account for the observed density contrast across the ICB. These indicate that silicon cannot be the sole light element in the core. Previous geochemical and cosmochemical arguments, however, strongly require ∼6 wt.% Si in the core. It is possible that the Earth's core originally included ∼6 wt.% Si but then became depleted in silicon by crystallizing SiO2 or MgSiO3.
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Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cho, Jongmin, E-mail: jongmin.cho@okstate.edu
2016-08-15
Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce radiosensitization through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer tomore » make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the {sup 66}Ga setting on a dose calibrator; activity decreased to 2 μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (2.05 × 10{sup 6} counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying {sup 66}Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. Conclusions: The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.« less
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Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers
Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun
2016-01-01
Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce radiosensitization through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the 66Ga setting on a dose calibrator; activity decreased to 2 μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (2.05 × 106 counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying 66Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. Conclusions: The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications. PMID:27487895
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Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers.
Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun
2016-08-01
Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce radiosensitization through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the (66)Ga setting on a dose calibrator; activity decreased to 2 μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (2.05 × 10(6) counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying (66)Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.
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Flexible, liquid core light guide with focusing and light shaping attachments
Wojcik, R.F.; Majewski, S.; Zorn, C.J.; Kross, B.
1999-04-20
A liquid light guide system for ultraviolet light is disclosed that has a light shaping arrangement for the emitted light, a stable liquid core and sheath and reliable and effective end closures. The end closures include a metal crimping arrangement that utilizes two layers of deformable materials to prevent cracking of endplugs. 19 figs.
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2016-09-01
AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances Radiosensitivity of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to
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5-(Halomethyl)uridine derivatives as potential antitumor radiosensitizers: A DFT study
NASA Astrophysics Data System (ADS)
Wang, Shoushan; Zhang, Min; Liu, Peng; Xie, Shilei; Cheng, Faliang; Wang, Lishi
2018-01-01
Considering the fact that the efficiency of the uridine-5-methyl radical in producing cytotoxic DNA intrastrand cross-link lesions is greatly higher than that of the uridine-5-yl radical, the radiosensitizing action of 5-(halomethyl)uridines (5-XCH2U, X = F, Cl, or Br) is studied in the present work. It is found that 5-XCH2U has sufficient electron affinity to capture a pre-hydrated or a hydrated electron, and electron attachment leads to significantly facile X- elimination forming the uridine-5-methyl radical. All these three halogenated uridine derivatives are shown to be potential radiosensitizers, with their radiosensitizing abilities increased in an order 5-FCH2U < 5-ClCH2U ≈ 5-BrCH2U.
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Mechanical and electro-optical properties of unconventional liquid crystal systems
NASA Astrophysics Data System (ADS)
Liao, Guangxun
Four types of unconventional liquid crystal systems - amphotropic glycolipids; novel bent-core liquid crystals, bent-core liquid crystal and glycolipid mixtures, and colloidal crystal-liquid crystal systems - were studied and characterized by polarizing microscopy, electrical current, digital scanning calorimetry, and dielectric spectroscopy. Thermotropic properties of glycolipids show a number of unusual properties, most notably high (60-120) relative dielectric constants mainly proportional to the number of polar sugar heads. The relaxation of this dielectric mode is found to be governed by the hydrogen bonding between sugar heads. Studies on novel bent-core liquid crystals reveal a new optically isotropic ferroelectric phase, molecular chirality-induced polarity, and transitions between molecular chirality and polarity driven phases. Mixtures of several bent-core substances with nematic, polar SmA and SmC phases, and a simple amphiphilic sugar lipid with SmA mesophase found to obey the well known miscibility rules, i.e. the sugar lipid mixes best with the polar SmA bent-core material. In addition, the chiral sugar lipid was found to induce tilt to the non-tilted polar SmA phase, which represents a new direction among the chirality--polarity--tilt relations. The effects of the surface properties and electric fields were studied on various colloid particles--and liquid crystal systems. It is found that the surface properties (hydrophobicity, roughness, rubbing) of the substrates are important in determining the size and symmetry of colloidal crystals. The director field of the liquid crystal infiltrated in the colloid crystals can be rendered both random and uniform along one of the crystallographic axis. We present the first observations of DC electric-field-induced rotational and translational motion of finite particles in liquid crystals. The electrorotation is essentially identical to the well - known Quincke rotation, which in liquid crystals triggers an additional translational motion at higher fields. Analysis of the electro-rotation and translations provides new ways to probe local rheological properties of liquid crystals.
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Integrated liquid-core optical fibers for ultra-efficient nonlinear liquid photonics.
Kieu, K; Schneebeli, L; Norwood, R A; Peyghambarian, N
2012-03-26
We have developed a novel integrated platform for liquid photonics based on liquid core optical fiber (LCOF). The platform is created by fusion splicing liquid core optical fiber to standard single-mode optical fiber making it fully integrated and practical - a major challenge that has greatly hindered progress in liquid-photonic applications. As an example, we report here the realization of ultralow threshold Raman generation using an integrated CS₂ filled LCOF pumped with sub-nanosecond pulses at 532 nm and 1064 nm. The measured energy threshold for the Stokes generation is 1nJ, about three orders of magnitude lower than previously reported values in the literature for hydrogen gas, a popular Raman medium. The integrated LCOF platform opens up new possibilities for ultralow power nonlinear optics such as efficient white light generation for displays, mid-IR generation, slow light generation, parametric amplification, all-optical switching and wavelength conversion using liquids that have orders of magnitude larger optical nonlinearities compared with silica glass.
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Cisplatin Radiosensitization of DNA Irradiated with 2-20 eV Electrons: Role of Transient Anions.
Bao, Qianhong; Chen, Yunfeng; Zheng, Yi; Sanche, Léon
2014-06-20
Platinum chemotherapeutic agents, such as cisplatin ( cis -diamminedichloroplatinum(II)), can act as radiosensitizers when bound covalently to nuclear DNA in cancer cells. This radiosensitization is largely due to an increase in DNA damage induced by low-energy secondary electrons, produced in large quantities by high-energy radiation. We report the yields of single- and double-strand breaks (SSB and DSB) and interduplex cross-links (CL) induced by electrons of 1.6-19.6 eV (i.e., the yield functions) incident on 5 monolayer (ML) films of cisplatin-DNA complexes. These yield functions are compared with those previously recorded with 5 ML films of unmodified plasmid DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base pairs) enhances SSB, DSB, and CL by factors varying, from 1.2 to 2.8, 1.4 to 3.5, and 1.2 to 2.7, respectively, depending on electron energy. All yield functions exhibit structures around 5 and 10 eV that can be attributed to enhancement of bond scission, via the initial formation of core-excited resonances associated with π → π * transitions of the bases. This increase in damage is interpreted as arising from a modification of the parameters of the corresponding transient anions already present in nonmodified DNA, particularly those influencing molecular dissociation. Two additional resonances, specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV in the yield function of SSB. Furthermore, cisplatin binding causes the induction of DSB by electrons of 1.6-3.6 eV, i.e., in an energy region where a DSB cannot be produced by a single electron in pure DNA. Breaking two bonds with a subexcitation-energy electron is tentatively explained by a charge delocalization mechanism, where a single electron occupies simultaneously two σ * bonds linking the Pt atom to guanine bases on opposite strands.
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Cisplatin Radiosensitization of DNA Irradiated with 2–20 eV Electrons: Role of Transient Anions
Bao, Qianhong; Chen, Yunfeng; Zheng, Yi; Sanche, Léon
2015-01-01
Platinum chemotherapeutic agents, such as cisplatin (cis-diamminedichloroplatinum(II)), can act as radiosensitizers when bound covalently to nuclear DNA in cancer cells. This radiosensitization is largely due to an increase in DNA damage induced by low-energy secondary electrons, produced in large quantities by high-energy radiation. We report the yields of single- and double-strand breaks (SSB and DSB) and interduplex cross-links (CL) induced by electrons of 1.6–19.6 eV (i.e., the yield functions) incident on 5 monolayer (ML) films of cisplatin–DNA complexes. These yield functions are compared with those previously recorded with 5 ML films of unmodified plasmid DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base pairs) enhances SSB, DSB, and CL by factors varying, from 1.2 to 2.8, 1.4 to 3.5, and 1.2 to 2.7, respectively, depending on electron energy. All yield functions exhibit structures around 5 and 10 eV that can be attributed to enhancement of bond scission, via the initial formation of core-excited resonances associated with π → π* transitions of the bases. This increase in damage is interpreted as arising from a modification of the parameters of the corresponding transient anions already present in nonmodified DNA, particularly those influencing molecular dissociation. Two additional resonances, specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV in the yield function of SSB. Furthermore, cisplatin binding causes the induction of DSB by electrons of 1.6–3.6 eV, i.e., in an energy region where a DSB cannot be produced by a single electron in pure DNA. Breaking two bonds with a subexcitation-energy electron is tentatively explained by a charge delocalization mechanism, where a single electron occupies simultaneously two σ* bonds linking the Pt atom to guanine bases on opposite strands. PMID:26793285
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard
Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.« less
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Zheng, Min; Morgan-Lappe, Susan E.; Yang, Jie; Bockbrader, Katrina M.; Pamarthy, Deepika; Thomas, Dafydd; Fesik, Stephen W.; Sun, Yi
2008-01-01
Radiotherapy combined with chemotherapy is the treatment of choice for glioblastoma and locally advanced lung cancer, but radioresistance of these two types of cancer remains a significant therapeutic hindrance. To identify molecular target(s) for radiosensitization, we screened a siRNA library targeting all protein kinases and E3 ubiquitin ligases in the human genome and identified TRAF2 (TNF Receptor-associated factor 2). Silencing of TRAF2 using siRNA caused a significant growth suppression of glioblastoma U251 cells and moderately sensitized these radioresistant cells to radiation. Overexpression of a RING deleted dominant negative TRAF2 mutant, also conferred radiosensitivity; whereas over-expression of wild type TRAF2 significantly protected cells from radiation-induced killing. Likewise, siRNA silencing of TRAF2 in radioresistant lung cancer H1299 cells caused growth suppression and radiosensitization, whereas overexpression of wild type TRAF2 enhanced radioresistance in a RING ligase-dependent manner. Moreover, siRNA silencing of TRAF2 in UM-SCC-1 head and neck cancer cells also conferred radiosensitization. Further support for the role of TRAF2 in cancer comes from the observations that TRAF2 is overexpressed in both lung adenocarcinoma tissues and multiple lung cancer cell lines. Importantly, TRAF2 expression was very low in normal bronchial epithelial NL20 cells, and TRAF2 silencing had a minimal effect on NL20 growth and radiation sensitivity. Mechanistically, TRAF2 silencing blocks the activation of the NF-kB signaling pathway, and down-regulates a number of G2/M cell cycle control proteins, resulting in enhanced G2/M arrest, growth suppression, and radiosensitization. Our studies suggest that TRAF2 is an attractive drug target for anti-cancer therapy and for radiosensitization. PMID:18794145
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dungey, Fiona A.; Loeser, Dana A.; Chalmers, Anthony J.
2008-11-15
Purpose: Current treatments for glioblastoma multiforme are inadequate and limited by the radiation sensitivity of normal brain. Because glioblastoma multiforme are rapidly proliferating tumors within nondividing normal tissue, the therapeutic ratio might be enhanced by combining radiotherapy with a replication-specific radiosensitizer. KU-0059436 (AZD2281) is a potent and nontoxic inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) undergoing a Phase II clinical trial as a single agent. Methods and Materials: Based on previous observations that the radiosensitizing effects of PARP inhibition are more pronounced in dividing cells, we investigated the mechanisms underlying radiosensitization of human glioma cells by KU-0059436, evaluating the replication dependence ofmore » this effect and its therapeutic potential. Results: KU-0059436 increased the radiosensitivity of four human glioma cell lines (T98G, U373-MG, UVW, and U87-MG). Radiosensitization was enhanced in populations synchronized in S phase and abrogated by concomitant exposure to aphidicolin. Sensitization was further enhanced when the inhibitor was combined with a fractionated radiation schedule. KU-0059436 delayed repair of radiation-induced DNA breaks and was associated with a replication-dependent increase in {gamma}H2AX and Rad51 foci. Conclusion: The results of our study have shown that KU-0059436 increases radiosensitivity in a replication-dependent manner that is enhanced by fractionation. A mechanism is proposed whereby PARP inhibition increases the incidence of collapsed replication forks after ionizing radiation, generating persistent DNA double-strand breaks. These observations indicate that KU-0059436 is likely to enhance the therapeutic ratio achieved by radiotherapy in the treatment of glioblastoma multiforme. A Phase I clinical trial is in development.« less
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Buchko, Garry W; Weinfeld, Michael
2002-09-01
The nitroimidazole-linked phenanthridines 2-NLP-3 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and 2-NLP-4 (5-[3-(2-nitro-1-imidazoyl)-butyl]-phenanthridinium bromide) are composed of the radiosensitizer, 2-nitroimidazole, attached to the DNA intercalator phenanthridine by a 3- and 4-carbon linker, respectively. Previous in vitro assays showed both compounds to be 10-100 times more efficient as hypoxic cell radiosensitizers (based on external drug concentrations) than the untargeted 2-nitroimidazole radiosensitizer, misonidazole (Cowan et al., Radiat. Res. 127, 81-89, 1991). Here we have used a (32)P postlabeling assay and 5'-end-labeled oligonucleotide assay to compare the radiation-induced DNA damage generated in the presence of 2-NLP-3, 2-NLP-4, phenanthridine and misonidazole. After irradiation of the DNA under anoxic conditions, we observed a significantly greater level of 3'-phosphoglycolate DNA damage in the presence of 2-NLP-3 or 2-NLP-4 compared to irradiation of the DNA in the presence of misonidazole. This may account at least in part for the greater cellular radiosensitization shown by the nitroimidazole-linked phenanthridines over misonidazole. Of the two nitroimidazole-linked phenanthridines, the better in vitro radiosensitizer, 2-NLP-4, generated more 3'-phosphoglycolate in DNA than did 2-NLP-3. At all concentrations, phenanthridine had little effect on the levels of DNA damage, suggesting that the enhanced radiosensitization displayed by 2-NLP-3 and 2-NLP-4 is due to the localization of the 2-nitroimidazole to the DNA by the phenanthridine substituent and not to radiosensitization by the phenanthridine moiety itself.
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Xu, Xiao-Ting; Hu, Wen-Tao; Zhou, Ju-Ying; Tu, Yu
2017-01-01
It has been reported that celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the radiosensitivity of several cancer cells. BCCIP (BRCA2 and CDKN1A interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the radiosensitivity of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the radiosensitivity of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-2 expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-2 negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced radiosensitivity of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H2AX foci formation, higher levels of radiation injury-related proteins phosphorylation, G2/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a radiosensitivity-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the radiosensitivity of HCT116 cells in a COX-2 independent manner. PMID:28386336
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Core-shell microspheres with porous nanostructured shells for liquid chromatography.
Ahmed, Adham; Skinley, Kevin; Herodotou, Stephanie; Zhang, Haifei
2018-01-01
The development of new stationary phases has been the key aspect for fast and efficient high-performance liquid chromatography separation with relatively low backpressure. Core-shell particles, with a solid core and porous shell, have been extensively investigated and commercially manufactured in the last decade. The excellent performance of core-shell particles columns has been recorded for a wide range of analytes, covering small and large molecules, neutral and ionic (acidic and basic), biomolecules and metabolites. In this review, we first introduce the advance and advantages of core-shell particles (or more widely known as superficially porous particles) against non-porous particles and fully porous particles. This is followed by the detailed description of various methods used to fabricate core-shell particles. We then discuss the applications of common silica core-shell particles (mostly commercially manufactured), spheres-on-sphere particles and core-shell particles with a non-silica shell. This review concludes with a summary and perspective on the development of stationary phase materials for high-performance liquid chromatography applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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The use of the term 'radiosensitivity' through history of radiation: from clarity to confusion.
Britel, Manon; Bourguignon, Michel; Foray, Nicolas
2018-05-01
The term 'radiosensitivity' appeared for the first time at the beginning of the 20th century, few years after the discovery of X-rays. Initially used by French and German radiologists, it illustrated the risk of radiation-induced (RI) skin reactions. From the 1950s, 'radiosensitivity' was progressively found to describe other features of RI response such as RI cancers or cataracts. To date, such confusion may raise legal issues and complexify the message addressed to general public. Here, through an historical review, we aimed to better understand how this confusion appeared. To support our historical review, a quantitative and qualitative wording analysis of the 'radiosensitivity' occurrences and its derived terms was performed with Google books, Pubmed, Web of Science™ databases, and in all the ICRP publications. While 'radiosensitivity' was historically related to RI adverse tissue events attributable to cell death, the first efforts to quantify the RI risk specific to each organ/tissue revealed some different semantic fields that are not necessarily compatible together (e.g. adverse tissue events for skin, cataracts for eyes, RI cancer for breast or thyroid). To avoid such confusion, we propose to keep the historical definition of 'radiosensitivity' to any clinical and cellular consequences of radiation attributable to cell death and to introduce the term 'radiosusceptibility' to describe the RI cancers or any feature that is attributable to cell transformation.
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Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun
Research highlights: {yields} In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. {yields} The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. {yields} The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. {yields} P53 status is not associated with the occurrence of unsensitized clone. {yields} Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeuticmore » regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC{sup -/-} cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC{sup -/-} clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti
Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratiomore » and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances radiosensitivity of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.« less
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Liquid-liquid phase separation of freely falling undercooled ternary Fe-Cu-Sn alloy
NASA Astrophysics Data System (ADS)
Wang, W. L.; Wu, Y. H.; Li, L. H.; Zhai, W.; Zhang, X. M.; Wei, B.
2015-11-01
The active modulation and control of the liquid phase separation for high-temperature metallic systems are still challenging the development of advanced immiscible alloys. Here we present an attempt to manipulate the dynamic process of liquid-liquid phase separation for ternary Fe47.5Cu47.5Sn5 alloy. It was firstly dispersed into numerous droplets with 66 ~ 810 μm diameters and then highly undercooled and rapidly solidified under the containerless microgravity condition inside drop tube. 3-D phase field simulation was performed to explore the kinetic evolution of liquid phase separation. Through regulating the combined effects of undercooling level, phase separation time and Marangoni migration, three types of separation patterns were yielded: monotectic cell, core shell and dispersive structures. The two-layer core-shell morphology proved to be the most stable separation configuration owing to its lowest chemical potential. Whereas the monotectic cell and dispersive microstructures were both thermodynamically metastable transition states because of their highly active energy. The Sn solute partition profiles of Fe-rich core and Cu-rich shell in core-shell structures varied only slightly with cooling rate.
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NASA Astrophysics Data System (ADS)
Tao, R.; Fei, Y.
2017-12-01
Planetary cooling leads to solidification of any initially molten metallic core. Some terrestrial cores (e.g. Mercury) are formed and differentiated under relatively reduced conditions, and they are thought to be composed of Fe-S-Si. However, there are limited understanding of the phase relations in the Fe-S-Si system at high pressure and temperature. In this study, we conducted high-pressure experiments to investigate the phase relations in the Fe-S-Si system up to 25 GPa. Experimental results show that the liquidus and solidus in this study are slightly lower than those in the Fe-S binary system for the same S concentration in liquid at same pressure. The Fe3S, which is supposed to be the stable sub-solidus S-bearing phase in the Fe-S binary system above 17 GPa, is not observed in the Fe-S-Si system at 21 GPa. Almost all S prefers to partition into liquid, while the distribution of Si between solid and liquid depends on experimental P and T conditions. We obtained the partition coefficient log(KDSi) by fitting the experimental data as a function of P, T and S concentration in liquid. At a constant pressure, the log(KDSi) linearly decreases with 1/T(K). With increase of pressure, the slopes of linear correlation between log(KDSi) and 1/T(K) decreases, indicating that more Si partitions into solid at higher pressure. In order to interpolate and extrapolate the phase relations over a wide pressure and temperature range, we established a comprehensive thermodynamic model in the Fe-S-Si system. The results will be used to constrain the distribution of S and Si between solid inner core and liquid outer core for a range of planet sizes. A Si-rich solid inner core and a S-rich liquid outer core are suggested for an iron-rich core.
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Cisplatin radiosensitizes radioresistant human mesenchymal stem cells.
Rühle, Alexander; Perez, Ramon Lopez; Glowa, Christin; Weber, Klaus-Josef; Ho, Anthony D; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E; Nicolay, Nils H
2017-10-20
Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.
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Radiosensitizing effects of neem (Azadirachta indica) oil.
Kumar, Ashok; Rao, A R; Kimura, H
2002-02-01
Radiosensitization by neem oil was studied using Balbc/3T3 cells and SCID cells. Neem oil enhanced the radiosensitivity of the cells when applied both during and after x-irradiation under aerobic conditions. Neem oil completely inhibited the repair of sublethal damage and potentially lethal damage repair in Balbc/3T3 cells. The cytofluorimeter data show that neem oil treatment before and after x-irradiation reduced the G(2) + M phase, thus inhibiting the expression of the radiation induced arrest of cells in the G(2) phase of the cell cycle. However, SCIK cells (derived from the SCID mouse), deficient in DSB repair, treated with neem oil did not show any enhancement in the radiosensitivity. There was no effect of neem oil on SLD repair or its inhibition in SCIK cells. These results suggest that neem oil enhanced the radiosensitivity of cells by interacting with residual damage after x-irradiation, thereby converting the sublethal damage or potentially lethal damage into lethal damage, inhibiting the double-strand break repair or reducing the G(2) phase of the cell cycle. Copyright 2002 John Wiley & Sons, Ltd.
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NASA Astrophysics Data System (ADS)
Buono, A. S.; Dasgupta, R.; Walker, D.
2011-12-01
Secular cooling of terrestrial planets is known to cause crystallization of a solid inner core from metallic liquid core. Fractionation of light and siderophile elements is important during such crystallization for evolution of outer core and possible core-mantle interaction. Thus far studies focused on a pure Fe inner core in simple binary systems but the effects of possible formation of a carbide inner core component on siderophile element partitioning in a multi-component system has yet to be looked at in detail. We investigated the effects of pressure and S content on partition coefficients (D) between cohenite and liquid in the Fe-Ni-S-C system. Multi-anvil experiments were performed at 3 and 6 GPa at 1150 °C, in an Fe-rich mix containing a constant C and Ni to which S contents of 0, 5, and 14 wt.% were added. All the mixes were doped with W, Re, Os, Pt, and Co. Samples were imaged and analyzed for Fe, Ni, S, and C using an EPMA. Fe, Ni, and trace elements were analyzed using a LA-ICP-MS. All the experiments produced cohenite and Fe-Ni-C±S liquid. Compared to solid-Fe/melt Ds [1-2], cohenite/melt Ds are lower for all elements except W. The light element (S+C) content of the liquid is the dominant controlling factor in siderophile element partitioning between cohenite and liquid as it is between crystalline Fe and liquid. In the cohenite-metallic melt experiments, D Ni decreases as S+C increases. Ni is excluded from the crystallizing solid if the solid is cohenite. We also find that in the Fe-Ni-S-C system, cohenite is stabilized to higher P than in the Fe-S-C system [3-5]. Similar to the Fe-metallic liquid systems the non-metal avoidance model [6] is applicable to the Fe3C-metallic liquid system studied here. Our study has implications for both the cores of smaller planets and the mantles of larger planets. If inner core forms a cohenite layer we would predict that depletions in the outer core will be less than they might be for Fe metal crystallization. For the mantle of the earth, which is thought to become Fe-Ni metal-saturated as shallow as 250 km, the sub-system Fe-Ni + C + S becomes relevant and Fe-Ni carbide rather than metallic Fe-Ni alloy may become the crystalline phase of interest. Our study implies that because the partition coefficients between cohenite and Fe-C-S melts are significantly lower than those between Fe-metal and S-rich liquid, in the presence of cohenite and Fe-C-S melt in the mantle, the mantle budget of Ni, Co, and Pt may be dominated by Fe-C-S liquid. W, Re, and Os will also be slightly enriched in C-rich Fe-Ni liquid over cohenite if the metal sub-system of interest is S-free. [1] Chabot et al., GCA 70, 1322-1335, 2006 [2] Chabot et al., GCA 72, 4146-4158, 2008 [3] Chabot et al., Meteorit. Planet. Sci. 42, 1735-1750, 2007 [4] Stewart et al., EPSL 284, 302-309, 2009 [5] Van Orman et al., EPSL 274, 250-257, 2008 [6] Jones, J.H., Malvin, D.J., Metall Mater Trans B 21, 697-706, 1990
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Evaluation of Radioresponse and Radiosensitizers in Glioblastoma Organotypic Cultures.
Bayin, N Sumru; Ma, Lin; Placantonakis, Dimitris G; Barcellos-Hoff, Mary Helen
2018-01-01
Glioblastoma (GBM), a deadly primary brain malignancy, manifests pronounced radioresistance. Identifying agents that improve the sensitivity of tumor tissue to radiotherapy is critical for improving patient outcomes. The response to ionizing radiation is regulated by both cell-intrinsic and -extrinsic mechanisms. In particular, the tumor microenvironment is known to promote radioresistance in GBM. Therefore, model systems used to test radiosensitizing agents need to take into account the tumor microenvironment. We recently showed that GBM explant cultures represent an adaptable ex vivo platform for rapid and personalized testing of radiosensitizers. These explants preserve the cellular composition and tissue architecture of parental patient tumors and therefore capture the microenvironmental context that critically determines the response to radiotherapy. This chapter focuses on the detailed protocol for testing candidate radiosensitizing agents in GBM explants.
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The Surface-Tension Method of Visually Inspecting Honeycomb-Core Sandwich Plates
NASA Technical Reports Server (NTRS)
Katzoff, Samuel
1960-01-01
When one face of a metal-honeycomb-core sandwich plate is heated or cooled relative to the other, heat transfer through the core causes the temperature on each face at the lines of contact with the core to be slightly different from that on the rest of the face. If a thin liquid film is applied to the face, the variation of surface tension with temperature causes the liquid to move from warmer to cooler areas and thus to develop a pattern corresponding to the temperature pattern on the face. Irregularities in the pattern identify the locations where the core is not adequately bonded to the face sheet. The pattern is easily observed when a fluorescent liquid is used and illumination is by means of ultraviolet light. Observation in ordinary light is also possible when a very deeply colored liquid is used. A method based on the use of a thermographic phosphor to observe the temperature pattern was found to be less sensitive than the surface-tension method. A sublimation method was found to be not only less sensitive but also far more troublesome.
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Interpretation of Core Length in Shear Coaxial Rocket Injectors from X-ray Radiography Measurements
2014-06-01
to the shape of the liquid jet core, elliptical EPL is what would be expected from a cylinder of liquid and has previously been observed in diesel...rely on the shear between an outer lower-density high velocity annulus and a higher- density low-velocity inner jet to atomize and mix a liquid and a...of combustion devices (turbofan engine exhaust, air blast furnaces, and liquid rocket engines) shear coaxial jets have been studied for over sixty
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Coated armor system and process for making the same
Chu, Henry S.; Lillo, Thomas M.; McHugh, Kevin M.
2010-11-23
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
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Optofluidic refractive-index sensor in step-index fiber with parallel hollow micro-channel.
Lee, H W; Schmidt, M A; Uebel, P; Tyagi, H; Joly, N Y; Scharrer, M; Russell, P St J
2011-04-25
We present a simple refractive index sensor based on a step-index fiber with a hollow micro-channel running parallel to its core. This channel becomes waveguiding when filled with a liquid of index greater than silica, causing sharp dips to appear in the transmission spectrum at wavelengths where the glass-core mode phase-matches to a mode of the liquid-core. The sensitivity of the dip-wavelengths to changes in liquid refractive index is quantified and the results used to study the dynamic flow characteristics of fluids in narrow channels. Potential applications of this fiber microstructure include measuring the optical properties of liquids, refractive index sensing, biophotonics and studies of fluid dynamics on the nanoscale.
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A low-threshold, high-efficiency microfluidic waveguide laser.
Vezenov, Dmitri V; Mayers, Brian T; Conroy, Richard S; Whitesides, George M; Snee, Preston T; Chan, Yinthai; Nocera, Daniel G; Bawendi, Moungi G
2005-06-29
This communication describes a long (1 cm), laser-pumped, liquid core-liquid cladding (L2) waveguide laser. This device provides a simple, high intensity, tunable light source for microfludic applications. Using a core solution of 2 mM rhodamine 640 perchlorate, optically pumped by a frequency-doubled Nd:YAG laser, we found that the threshold for lasing was as low as 22 muJ (16-ns pulse length) and had a slope efficiency up to 20%. The output wavelength was tunable over a 20-nm range by changing the ratio of solvent components (dimethyl sulfoxide and methanol) in the liquid core.
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Field alignment of bent-core smectic liquid crystals for analog optical phase modulation
NASA Astrophysics Data System (ADS)
Shen, Y.; Goodhew, L.; Shao, R.; Moran, M.; Korblova, E.; Walba, D. M.; Clark, N. A.; Maclennan, J. E.; Rudquist, P.
2015-05-01
A general method for aligning bent-core smectic liquid crystal materials is described. Alternating electric fields between interdigitated electrodes patterned on one cell surface create torques on the liquid crystal that result in uniform "bookshelf" orientation of the smectic layers. The aligned cell can then be driven in the conventional way by applying an electric field between all of the stripe electrodes connected together and a monolithic electrode on the other cell surface. Fast, analog, optical phase-only modulation is demonstrated in a device containing a polar, bent-core SmAPF material aligned using this technique.
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Sound velocity of Fe-S liquids at high pressure: Implications for the Moon's molten outer core
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jing, Zhicheng; Wang, Yanbin; Kono, Yoshio
2014-07-21
Sound velocities of Fe and Fe–S liquids were determined by combining the ultrasonic measurements and synchrotron X-ray techniques under high pressure–temperature conditions from 1 to 8 GPa and 1573 K to 1973 K. Four different liquid compositions were studied including Fe, Fe–10 wt% S, Fe–20 wt% S, and Fe–27 wt% S. Our data show that the velocity of Fe-rich liquids increases upon compression and decreases with increasing sulfur content, whereas temperature has negligible effect on the velocity of Fe–S liquids. The sound velocity data were combined with ambient-pressure densities to fit the Murnaghan equation of state (EOS). Compared to themore » lunar seismic model, our velocity data constrain the sulfur content at 4±3 wt%, indicating a significantly denser (6.5±0.5 g/cm 3) and hotter (1870-70+100 K) outer core than previously estimated. A new lunar structure model incorporating available geophysical observations points to a smaller core radius. Our model suggests a top–down solidification scenario for the evolution of the lunar core. Such “iron snow” process may have been an important mechanism for the growth of the inner core.« less
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NASA Astrophysics Data System (ADS)
Lim, Sara N.; Pradhan, Anil K.; Nahar, Sultana N.; Barth, Rolf F.; Yang, Weilian; Nakkula, Robin J.; Palmer, Alycia; Turro, Claudia
2013-06-01
High energy X-rays in the MeV range are generally employed in conventional radiation therapy from linear accelerators (LINAC) to ensure sufficient penetration depths. However, lower energy X-rays in the keV range may be more effective when coupled with heavy element (high-Z or HZ) radiosensitizers. Numerical simulations of X-ray energy deposition for tumor phantoms sensitized with HZ radiosensitizers were performed using the Monte Carlo code Geant4. The results showed enhancement in energy deposition to radiosensitized phantoms relative to unsensitized phantoms for low energy X-rays in the keV range. In contrast, minimal enhancement was seen using high energy X-rays in the MeV range. Dose enhancement factors (DEFs) were computed and showed radiosensitization only in the low energy range < 200 keV, far lower than the energy of the majority of photons in the LINAC energy range. In vitro studies were carried to demonstrate the tumoricidal effects of HZ sensitized F98 rat glioma cells following irradiation with both low energy 160 kV and high energy 6 MV X-ray sources. The platinum compound, pyridine terpyridine Pt(II) nitrate, was initially used because it was 7x less toxic that an equivalent amount of carboplatin in vitro studies. This would allow us to separate the radiotoxic and the chemotoxic effects of HZ sensitizers. Results from this study showed a 10-fold dose dependent reduction in surviving fractions (SF) of radiosensitized cells treated with low energy 160 kV X-rays compared to those treated with 6 MV X-rays. This is in agreement with our simulations that show an increase in dose deposition in radiosensitized tumors for low energy X-rays. Due to unforeen in vivo toxicity, however, another in vitro study was performed using the commonly used, Pt-based chemotherapeutic drug carboplatin which confirmed earlier results. This lays the ground work for a planned in vivo study using F98 glioma bearing rats. This study demonstrates that while high energy X-rays are commonly used in cancer radiotherapy, low energy keV X-rays might be much more effective with HZ radiosensitization.
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Simultaneous Inhibition of EGFR and PI3K Enhances Radiosensitivity in Human Breast Cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li Ping; Zhang Qing; Torossian, Artour
2012-07-01
Purpose: Mutations in the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling transduction pathway are common in cancer. This pathway is imperative to the radiosensitivity of cancer cells. We aimed to investigate the radiosensitizing effects of the simultaneous inhibition of EGFR and PI3K in breast cancer cells. Methods and Materials: MCF-7 cell lines with low expression of EGFR and wild-type PTEN and MDA-MB-468 cell lines with high expression of EGFR and mutant PTEN were used. The radiosensitizing effects by the inhibition of EGFR with AG1478 and/or PI3K with Ly294002 were determined by colony formation assay, Western blot was used tomore » investigate the effects on downstream signaling. Flow cytometry was used for apoptosis and cell cycle analysis. Mice-bearing xenografts of MDA-MB-468 breast cancer cells were also used to observe the radiosensitizing effect. Results: Simultaneous inhibition of EGFR and PI3K greatly enhanced radiosensitizing effect in MDA-MB-468 in terms of apoptosis and mitotic death, either inhibition of EGFR or PI3K alone could enhance radiosensitivity with a dose-modifying factor (DMF{sub SF2}) of 1.311 and 1.437, radiosensitizing effect was further enhanced by simultaneous inhibition of EGFR and PI3K with a DMF{sub SF2} at 2.698. DNA flow cytometric analysis indicated that dual inhibition combined with irradiation significantly induced G0/G1 phase arrest in MDA-MB-468 cells. The expression of phosphor-Akt and phosphor-Erk1/2 (induced by irradiation and PI3K inhibitor) were fully attenuated by simultaneous treatment with both inhibitors in combination with irradiation. In addition, dual inhibition combined with irradiation induced dramatic tumor growth delay in MDA-MB-468 xenografts. Conclusions: Our study indicated that simultaneous inhibition of EGFR and PI3K could further sensitize the cancer cells to irradiation compared to the single inhibitor with irradiation in vitro and in vivo. The approach may have important therapeutic implication in the treatment of a subset of breast cancer patients with high expression of EGFR and deficient function of PTEN.« less
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Si-depleted outer core inferred from sound velocity measurements of liquid Fe-Si alloys
NASA Astrophysics Data System (ADS)
Nakajima, Y.; Imada, S.; Hirose, K.; Kuwayama, Y.; Sinmyo, R.; Tateno, S.; Ozawa, H.; Tsutsui, S.; Uchiyama, H.; Baron, A. Q. R.
2016-12-01
Recent core formation models [1,2] suggested that a large amount of Si could have been incorporated into the core forming metals in the early stage of the Earth. These studies gave estimates for the Si content in the core, from 2 to 9 wt.%. In order to constrain the Si content of the outer core, we have determined the sound wave velocity of liquid Fe-Si alloys under high pressures and high temperatures. Starting materials of Fe-Si alloys with 6.5 and 9 wt.% Si were melted in a laser-heated diamond-anvil cell. The longitudinal acoustic phonon excitation of a liquid metal was measured up to 52 GPa and 3200 K by using high resolution inelastic X-ray scattering spectroscopy at beamline BL35XU [3] of the SPring-8 synchrotron facility. Our results show that silicon significantly increases the P-wave velocity of liquid Fe. Seismological observation shows that the P-wave velocity in the outer core is 3-4% faster than in pure iron. Comparing the present results with seismological observations, the silicon content of the outer core should be limited to be <2 wt.%, significantly lower than previous estimates based on the element partitioning between core forming mental and silicate magma ocean during core formation processes. This indicates that the present-day core is depleted in Si relative to the ancient core just after core formation, which agrees with the recent proposal [4] that the Si content in the outer core has been diminished by SiO2 crystallization through the core cooling history. [1] Rubie et al. (2011) Earth Planet. Sci. Lett. 301, 31-42. [2] Siebert et al. (2013) Science 339, 1194-1197. [3] Baron et al. (2000) J. Phys. Chem. Solids 61, 461-465 [4] Hirose et al. (2015) Abstract presented at AGU Fall Meeting 2015.
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Insights into Mercury's interior structure from geodesy measurements and global contraction
NASA Astrophysics Data System (ADS)
Rivoldini, A.; Van Hoolst, T.
2014-04-01
The measurements of the gravitational field of Mercury by MESSENGER [6] and improved measurements of the spin state of Mercury [3] provide important insights on its interior structure. In particular, these data give strong constraints on the radius and density of Mercury's core [5, 2]. However, present geodesy data do not provide strong constraints on the radius of the inner core. The data allow for models with a fully molten liquid core to models which have an inner core radius that is smaller than about 1760km [5], if it is assumed that sulfur is the only light element in the core. Models without an inner core are, however, at odds with the observed internally generated magnetic field of Mercury since Mercury's dynamo cannot operate by secular cooling alone at present. The present radius of the inner core depends mainly on Mercury's thermal state and light elements inside the core. Because of the secular cooling of the planet,the temperature inside the core drops below the liquidus temperature of the core material somewhere in the core and leads to the formation of an inner core and to the global contraction of the planet. The amount of contraction depends on the temperature decrease, on the thermal expansion of the materials inside the planet, and on the volume of crystallized liquid core alloy. In this study we use geodesy data, the recent estimate about the radial contraction of Mercury [1], and thermo-chemical evolution calculations in order to improve our knowledge about Mercury's inner core radius and thermal state. Since data from remote sensing of Mercury's surface [4] indicate that Mercury formed under reducing conditions we consider models that have sulfur and silicon as light elements inside their core. Unlike sulfur, which does almost not partition into solid iron under Mercury's core pressure and temperature conditions, silicon partitions virtually equally between solid and liquid iron. As a consequence, the density difference between the liquid and the crystallized material is smaller than for sulfur as only light element inside the core and therefore, for a given inner core radius the contraction of the planet is likely smaller.
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A tunable optofluidic circular liquid fiber
NASA Astrophysics Data System (ADS)
Li, Lei; Wu, Wei; Shi, Yang; Gong, Enze; Yang, Yi
2016-01-01
This paper presents a tunable optofluidic circular liquid fiber through the numerical simulation. Fiber is a significant optical device and has been widely applied on optical fiber communication. But the fiber based solid has limited tunability. Compared to solid fiber, the fiber based liquid material is relatively infrequent. Cause for the liquid optical device has more freedom tunable properties than solid counterpart, it has attracted more interest. The traditional optofluidic waveguide is designed like a sandwich in planar channel. This two-dimensional (2D) structure liquid waveguide will face huge transmission loss in the perpendicular direction of the flow streams. In this paper, a curving microchannel is designed inside the microchip to produce centrifugal effect. Two different liquids are injected into the chip by external pumps. In a particular situation, the core flow will be totally surrounded by the cladding flow. So the liquid can form an optical waveguide. Its structure is similar to an optical fiber which high refractive index (RI) liquid is core of the waveguide and the low RI liquid is cladding of the waveguide. Profit from the reconfigurability of liquid material, this liquid fiber has excellent tunability. The diameter of the core flow can be tuned in a wider range by changing the volume ratio of the flows through the finite element analysis. It is predictable that such a tunable liquid fiber may find wider applications in lab-on-a-chip systems and integrated optical devices.
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Chen, Xuwei; Yang, Xu; Zeng, Wanying; Wang, Jianhua
2015-08-04
Protein transfer from aqueous medium into ionic liquid is an important approach for the isolation of proteins of interest from complex biological samples. We hereby report a solid-cladding/liquid-core/liquid-cladding sandwich optical waveguide system for the purpose of monitoring the dynamic mass-transfer behaviors of hemoglobin (Hb) at the aqueous/ionic liquid interface. The optical waveguide system is fabricated by using a hydrophobic IL (1,3-dibutylimidazolium hexafluorophosphate, BBimPF6) as the core, and protein solution as one of the cladding layer. UV-vis spectra are recorded with a CCD spectrophotometer via optical fibers. The recorded spectra suggest that the mass transfer of Hb molecules between the aqueous and ionic liquid media involve accumulation of Hb on the aqueous/IL interface followed by dynamic extraction/transfer of Hb into the ionic liquid phase. A part of Hb molecules remain at the interface even after the accomplishment of the extraction/transfer process. Further investigations indicate that the mass transfer of Hb from aqueous medium into the ionic liquid phase is mainly driven by the coordination interaction between heme group of Hb and the cationic moiety of ionic liquid, for example, imidazolium cation in this particular case. In addition, hydrophobic interactions also contribute to the transfer of Hb.
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The ab initio simulation of the Earth's core.
Alfè, D; Gillan, M J; Vocadlo, L; Brodholt, J; Price, G D
2002-06-15
The Earth has a liquid outer and solid inner core. It is predominantly composed of Fe, alloyed with small amounts of light elements, such as S, O and Si. The detailed chemical and thermal structure of the core is poorly constrained, and it is difficult to perform experiments to establish the properties of core-forming phases at the pressures (ca. 300 GPa) and temperatures (ca. 5000-6000 K) to be found in the core. Here we present some major advances that have been made in using quantum mechanical methods to simulate the high-P/T properties of Fe alloys, which have been made possible by recent developments in high-performance computing. Specifically, we outline how we have calculated the Gibbs free energies of the crystalline and liquid forms of Fe alloys, and so conclude that the inner core of the Earth is composed of hexagonal close packed Fe containing ca. 8.5% S (or Si) and 0.2% O in equilibrium at 5600 K at the boundary between the inner and outer cores with a liquid Fe containing ca. 10% S (or Si) and 8% O.
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Core body temperature control by total liquid ventilation using a virtual lung temperature sensor.
Nadeau, Mathieu; Micheau, Philippe; Robert, Raymond; Avoine, Olivier; Tissier, Renaud; Germim, Pamela Samanta; Vandamme, Jonathan; Praud, Jean-Paul; Walti, Herve
2014-12-01
In total liquid ventilation (TLV), the lungs are filled with a breathable liquid perfluorocarbon (PFC) while a liquid ventilator ensures proper gas exchange by renewal of a tidal volume of oxygenated and temperature-controlled PFC. Given the rapid changes in core body temperature generated by TLV using the lung has a heat exchanger, it is crucial to have accurate and reliable core body temperature monitoring and control. This study presents the design of a virtual lung temperature sensor to control core temperature. In the first step, the virtual sensor, using expired PFC to estimate lung temperature noninvasively, was validated both in vitro and in vivo. The virtual lung temperature was then used to rapidly and automatically control core temperature. Experimentations were performed using the Inolivent-5.0 liquid ventilator with a feedback controller to modulate inspired PFC temperature thereby controlling lung temperature. The in vivo experimental protocol was conducted on seven newborn lambs instrumented with temperature sensors at the femoral artery, pulmonary artery, oesophagus, right ear drum, and rectum. After stabilization in conventional mechanical ventilation, TLV was initiated with fast hypothermia induction, followed by slow posthypothermic rewarming for 1 h, then by fast rewarming to normothermia and finally a second fast hypothermia induction phase. Results showed that the virtual lung temperature was able to provide an accurate estimation of systemic arterial temperature. Results also demonstrate that TLV can precisely control core body temperature and can be favorably compared to extracorporeal circulation in terms of speed.
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Cheng, Yanlei; Li, Fanghua; Mladenov, Emil; Iliakis, George
2015-09-01
The radiosensitivity to killing of tumor cells and in-field normal tissue are key determinants of radiotherapy response. In vitro radiosensitivity of tumor- and normal-tissue-derived cells often predicts radiation response, but high determination cost in time and resources compromise utility as routine response-predictor. Efforts to use induction or repair of DNA double-strand-breaks (DSBs) as surrogate-predictors of cell radiosensitivity to killing have met with limited success. Here, we re-visit this issue encouraged by our recent observations that ionizing radiation (IR) induces not only promptly-forming DSBs (prDSBs), but also DSBs developing after irradiation from the conversion to breaks of thermally-labile sugar-lesions (tlDSBs). We employ pulsed-field gel-electrophoresis and flow-cytometry protocols to measure total DSBs (tDSB=prDSB+tlDSBs) and prDSBs, as well as γH2AX and parameters of chromatin structure. We report a fully unexpected and in many ways unprecedented correlation between yield of prDSBs and radiosensitivity to killing in a battery of ten tumor cell lines that is not matched by yields of tDSBs or γH2AX, and cannot be explained by simple parameters of chromatin structure. We propose the introduction of prDSBs-yield as a novel and powerful surrogate-predictor of cell radiosensitivity to killing with potential for clinical application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Enhancement of recombinant myricetin on the radiosensitivity of lung cancer A549 and H1299 cells
2014-01-01
Objective Myricetin, a common dietary flavonoid is widely distributed in fruits and vegetables, and is used as a health food supplement based on its immune function, anti-oxidation, anti-tumor, and anti-inflammatory properties. The aim of this study was to investigate the effects of myricetin on combination with radiotherapy enhance radiosensitivity of lung cancer A549 and H1299 cells. Methods A549 cells and H1299 cells were exposed to X-ray with or without myricetin treatment. Colony formation assays, CCK-8 assay, flow cytometry and Caspase-3 level detection were used to evaluate the radiosensitization activity of myricetin on cell proliferation and apoptosis in vitro. Nude mouse tumor xenograft model was built to assessed radiosensitization effect of myricetin in vivo. Results Compared with the exposed group without myricetin treatment, the groups treated with myricetin showed significantly suppressed cell surviving fraction and proliferation, increased the cell apoptosis and increased Caspase-3 protein expression after X-ray exposure in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in irradiated mice treated with myricetin. Conclusions The study demonstrated both in vitro and in vivo evidence that combination of myricetin with radiotherapy can enhance tumor radiosensitivity of pulmonary carcinoma A549 and H1299 cells, and myricetin could be a potential radiosensitizer for lung cancer therapy. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5791518001210633 PMID:24650056
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Coco-Martin, J M; Ottenheim, C P; Bartelink, H; Begg, A C
1996-03-01
In order to find an explanation for the eventual disappearance of all chromosome aberrations in two radiosensitive human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two radiosensitive and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two radiosensitive lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or G1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for radiosensitivity.
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Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko
2015-01-01
KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300. PMID:26716455
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Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko
2015-01-01
KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300.
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Xu, Wen-Hong; Han, Min; Dong, Qi; Fu, Zhi-Xuan; Diao, Yuan-Yuan; Liu, Hai; Xu, Jing; Jiang, Hong-Liang; Zhang, Su-Zhan; Zheng, Shu; Gao, Jian-Qing; Wei, Qi-Chun
2012-01-01
Background The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. Methods A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. Results Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. Conclusion Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer. PMID:22679376
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Multiple Experimental Efforts to Understand the Structure and Dynamics of Earth's Core
NASA Astrophysics Data System (ADS)
Fei, Y.; Han, L.; Bennett, N.; Hou, M.; Kuwayama, Y.; Huang, H.
2014-12-01
It requires integration of data from different types of high-pressure experiments to understand the structure and dynamics of Earth's core. In particular, measurements of physical properties and element partitioning in systems relevant to the core provide complementary data to narrow down the range of possible core compositions. We have performed both static and dynamic compression experiments and combined results from these with literature data to establish a reliable thermal equation of state of iron. This allows us to precisely determine the density deficit in the solid inner core. The combination of density and sound velocity measurements for both solid and liquid iron and its alloys provide tight constraints on the density deficit in the liquid outer core and the amount of sulphur required to match the geophysical observations. We then conducted element-partitioning experiments between solid and liquid iron in both multi-anvil apparatus and the laser-heated diamond-anvil cell to determine the sulphur, silicon, and oxygen partitioning between the liquid outer core and solid inner core. We present newly developed high-pressure experimental and nano-scale analytical techniques that allow us to simulate the conditions of the inner core boundary (ICB) and analyze the chemical compositions of coexisting phases in the recovered samples. We have established protocols to obtain high-quality partitioning data in the laser-heating diamond-anvil cell combined with FIB/SEM crossbeam technology. The partitioning data obtained up to at least 200 GPa provide additional criteria to explain the observed density and velocity jumps at the ICB.
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NASA Astrophysics Data System (ADS)
Murrell, M. T.; Burnett, D. S.
1986-07-01
The possibility of heating of planetary cores by K radioactivity has been extensively discussed, as well as the possibility that K partitioning into the terrestrial core is the reason for the difference between the terrestrial and chondritic K/U. We had previously suggested that U and Th partitioning into FeFeS liquids was more important than K. Laboratory FeFeS liquid, silicate liquid partition coefficient measurements (D) for K, U, and Th were made to test this suggestion. For a basaltic liquid at 1450°C and 1.5 GPa, DU is 0.013 and DK is 0.0026; thus U partitioning into FeFeS liquids is 5 times greater than K partitioning under these conditions. There are problems with 1-atm experiments in that they do not appear to equilibrate or reverse. However, measurable U and Th partitioning into sulfide was nearly always observed, but K partitioning was normally not observed (DK <~ 10-4). A typical value for DU from a granitic silicate liquid at one atmosphere, 1150°C, and low f02 is about 0.02; DTh is similar. At low f02 and higher temperature, experiments with basaltic liquids produce strong Ca and U partitioning into the sulfide liquid with DU > 1. DTh is less strongly affected. Because of the consistently low DK/DU, pressure effects near the core-mantle boundary would need to increase DK by factors of ~103 with much smaller increases in DU in order to have the terrestrial K and U abundances at chondritic levels. In addition, if radioactive heating is important for planetary cores, U and Th will be more important than K unless the lower mantle has K/U greater than 10 times chondritic or large changes in partition coefficients with conditions reverse the relative importance of K versus U and Th from our measurements.
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Nonlinear saturation of the Rayleigh instability due to oscillatory flow in a liquid-lined tube
NASA Astrophysics Data System (ADS)
Halpern, David; Grotberg, James B.
2003-10-01
In this paper, the stability of core annular flows consisting of two immiscible fluids in a cylindrical tube with circular cross-section is examined. Such flows are important in a wide range of industrial and biomedical applications. For example, in secondary oil recovery, water is pumped into the well to displace the remaining oil. It is also of relevance in the lung, where a thin liquid film coats the inner surface of the small airways of the lungs. In both cases, the flow is influenced by a surface-tension instability, which may induce the breakup of the core fluid into short plugs, reducing the efficiency of the oil recovery, or blocking the passage of air in the lung thus inducing airway closure. We consider the stability of a thin film coating the inner surface of a rigid cylindrical tube with the less viscous fluid in the core. For thick enough films, the Rayleigh instability forms a liquid bulge that can grow to eventually create a plug blocking the tube. The analysis explores the effect of an oscillatory core flow on the interfacial dynamics and particularly the nonlinear stabilization of the bulge. The oscillatory core flow exerts tangential and normal stresses on the interface between the two fluids that are simplified by uncoupling the core and film analyses in the thin-film high-frequency limit of the governing equations. Lubrication theory is used to derive a nonlinear evolution equation for the position of the air liquid interface which includes the effects of the core flow. It is shown that the core flow can prevent plug formation of the more viscous film layer by nonlinear saturation of the capillary instability. The stabilization mechanism is similar to that of a reversing butter knife, where the core shear wipes the growing liquid bulge back on to the tube wall during the main tidal volume stroke, but allows it to grow back as the stoke and shear turn around. To be successful, the leading film thickness ahead of the bulge must be smaller than the trailing film thickness behind it, a requirement necessitating a large enough core capillary number which promotes a large core shear stress on the interface. The core capillary number is defined to be the ratio of core viscous forces to surface tension forces. When this process is tuned correctly, the two phases balance and there is no net growth of the liquid bulge over one cycle. We find that there is a critical frequency above which plug formation does not occur, and that this critical frequency increases as the tidal volume amplitude of the core flow decreases.
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Biconcave micro-optofluidic lens with low-refractive-index liquids.
Song, Chaolong; Nguyen, Nam-Trung; Asundi, Anand Krishna; Low, Cassandra Lee-Ngo
2009-12-01
One of the current problems of micro-optofluidics is the choice of a suitable liquid with a high refractive index (RI). We report the use of a low-RI liquid in a biconcave liquid-core liquid-cladding lens for focusing light. For the characterization of the lens, a telescope system was constructed from polydimethylsiloxane lenses to collimate and expand a light beam emitted from an optical fiber. The tunable optofluidic biconcave lens focuses the parallel beam. Fluorescent dye diluted in an index-matching liquid was used for the visualization of the light rays in a beam-tracing chamber. The focused beam is tuned by adjusting the flow rate ratio between core and cladding streams.
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ERIC Educational Resources Information Center
Jeanloz, Raymond
1983-01-01
The nature of the earth's core is described. Indirect evidence (such as that determined from seismological data) indicates that it is an iron alloy, solid toward its center but otherwise liquid. Evidence also suggests that it is the turbulent flow of the liquid that generates the earth's magnetic field. (JN)
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Methods of producing armor systems, and armor systems produced using such methods
Chu, Henry S; Lillo, Thomas M; McHugh, Kevin M
2013-02-19
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
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NASA Astrophysics Data System (ADS)
Shimoyama, Yuta; Terasaki, Hidenori; Urakawa, Satoru; Takubo, Yusaku; Kuwabara, Soma; Kishimoto, Shunpachi; Watanuki, Tetsu; Machida, Akihiko; Katayama, Yoshinori; Kondo, Tadashi
2016-11-01
Carbon is one of the possible light elements in the cores of the terrestrial planets. The P wave velocity (VP) and density (ρ) are important factors for estimating the chemical composition and physical properties of the core. We simultaneously measured the VP and ρ of Fe-3.5 wt % C up to 3.4 GPa and 1850 K by using ultrasonic pulse-echo method and X-ray absorption methods. The VP of liquid Fe-3.5 wt % C decreased linearly with increasing temperature at constant pressure. The addition of carbon decreased the VP of liquid Fe by about 2% at 3 GPa and 1700 K and decreased the Fe density by about 2% at 2 GPa and 1700 K. The bulk modulus of liquid Fe-C and its pressure (P) and temperature (T) effects were precisely determined from directly measured ρ and VP data to be K0,1700 K = 83.9 GPa, dKT/dP = 5.9(2), and dKT/dT = -0.063 GPa/K. The addition of carbon did not affect the isothermal bulk modulus (KT) of liquid Fe, but it decreased the dK/dT of liquid Fe. In the ρ-VP relationship, VP increases linearly with ρ and can be approximated as VP (m/s) = -6786(506) + 1537(71) × ρ (g/cm3), suggesting that Birch's law is valid for liquid Fe-C at the present P-T conditions. Our results imply that at the conditions of the lunar core, the elastic properties of an Fe-C core are more affected by temperature than those of Fe-S core.
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Rezaee, Zohre; Yadollahpour, Ali; Bayati, Vahid; Negad Dehbashi, Fereshteh
2017-01-01
Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of radiosensitizers to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy. Radiosensitizing effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR. Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, 2.61, and 2.89, indicating synergistic radiosensitizing effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines. Combined GNPs-EP protocols induced synergistic radiosensitizing effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less radiosensitive tumors.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Plataniotis, George A.; Dale, Roger G.
2008-12-01
Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell killmore » as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.« less
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Iron snow in the Martian core?
NASA Astrophysics Data System (ADS)
Davies, Christopher J.; Pommier, Anne
2018-01-01
The decline of Mars' global magnetic field some 3.8-4.1 billion years ago is thought to reflect the demise of the dynamo that operated in its liquid core. The dynamo was probably powered by planetary cooling and so its termination is intimately tied to the thermochemical evolution and present-day physical state of the Martian core. Bottom-up growth of a solid inner core, the crystallization regime for Earth's core, has been found to produce a long-lived dynamo leading to the suggestion that the Martian core remains entirely liquid to this day. Motivated by the experimentally-determined increase in the Fe-S liquidus temperature with decreasing pressure at Martian core conditions, we investigate whether Mars' core could crystallize from the top down. We focus on the "iron snow" regime, where newly-formed solid consists of pure Fe and is therefore heavier than the liquid. We derive global energy and entropy equations that describe the long-timescale thermal and magnetic history of the core from a general theory for two-phase, two-component liquid mixtures, assuming that the snow zone is in phase equilibrium and that all solid falls out of the layer and remelts at each timestep. Formation of snow zones occurs for a wide range of interior and thermal properties and depends critically on the initial sulfur concentration, ξ0. Release of gravitational energy and latent heat during growth of the snow zone do not generate sufficient entropy to restart the dynamo unless the snow zone occupies at least 400 km of the core. Snow zones can be 1.5-2 Gyrs old, though thermal stratification of the uppermost core, not included in our model, likely delays onset. Models that match the available magnetic and geodetic constraints have ξ0 ≈ 10% and snow zones that occupy approximately the top 100 km of the present-day Martian core.
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Repurposing cephalosporin antibiotics as pro-senescent radiosensitizers.
Labay, Edwardine; Mauceri, Helena J; Efimova, Elena V; Flor, Amy C; Sutton, Harold G; Kron, Stephen J; Weichselbaum, Ralph R
2016-06-07
Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with radiosensitizers. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust radiosensitization in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic radiosensitizers to enhance the therapeutic ratio of radiotherapy.
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Radiosensitivity of different tissues from carrot root at different phases of growth in culture
DOE Office of Scientific and Technical Information (OSTI.GOV)
Degani, N.; Pickholtz, D.
1980-09-01
The present work compares the effect of ..gamma..-radiation dose and time in culture on the growth of cambium and phloem carrot (Daucus carota) root explants. It was found that the phloem is more radiosensitive than the cambium and that both tissues were more radiosensitive when irradiated on excision at the G/sub 1/ phase rather than at the end of the lag phase on the ninth day of growth in culture when cells were predominantly at the G/sub 2/ phase. The nuclear volumes of cells from both tissues were similar but were larger at the end of the more radioresistant lagmore » phase than those of the G/sub 1/ phase on excision. However, nuclear volume could not account for the differences in radiosensitivity between either the tissues or irradiation times in culture.« less
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Chen, Feng; Zhang, Xiao Hong; Hu, Xiao Dan; Liu, Pei Dang; Zhang, Hai Qian
2018-08-01
Radiosensitizers that increase cancer cell radio-sensitivity can enhance the effectiveness of irradiation and minimize collateral damage. Nanomaterial has been employed in conjunction with radiotherapy as radiosensitizers, due to its unique physicochemical properties. In this article, we evaluated selenium nanoparticles (Nano-Se) as a new radiosensitizer. Nano-Se was used in conjunction with irradiation on MCF-7 breast cancer cells, and efficacy and mechanisms of this combined treatment approach were evaluated. Nano-Se reinforced the toxic effects of irradiation, leading to a higher mortality rate than either treatment used alone, inducing cell cycle arrest at the G2/M phase and the activation of autophagy, and increasing both endogenous and irradiation-induced reactive oxygen species formation. These results suggest that Nano-Se can be used as an adjuvant drug to improve cancer cell sensitivity to the toxic effects of irradiation and thereby reduce damage to normal tissue nearby.
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Impact of material absorption on supercontinuum generation in liquid core photonic crystal fiber
NASA Astrophysics Data System (ADS)
Nithyanandan, K.; Raja, Vasantha Jayakantha; Uthayakumar, T.; Porsezian, K.
2013-06-01
The impact of material absorption on supercontinuum generation (SCG) in liquid core photonic crystal fiber (LCPCF) is presented. While PCFs with cores made from different glasses are well studied in previous works with saturable nonlinear response (SNL), in this paper, it is planned to investigate the dynamics of nonlinear processes of supercontinuum generation in high-index fiber with material absorption to understand the physical phenomena of pulse propagation.
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Alkyl Chain Ordering of Asymmetric Phosphatidyicholines Adsorbed at a Liquid-Liquid Interface
1998-05-30
the blood bind to the PL surface and begin to hydrolyze the triglyceride core and only a small fraction of the phospholipids, such that the core...which surface-adsorbed proteins are able to hydrolyze the triglyceride core has been shown to depend on the acyl chain composition of monolayer PCs...in the commercial use of natural phosphatidylcholines (or lecithins ) as emulsifiers, including their use in delivery of water-insoluble drugs (Davis
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Si and O partitioning between core metal and lower mantle minerals during core formation
NASA Astrophysics Data System (ADS)
Nakajima, Y.; Frost, D. J.; Rubie, D. C.
2010-12-01
In addition to Fe and Ni, the Earth’s core contains light alloying elements (e.g., H, C, O, Si, and/or S) in order to explain the 10% core density deficit (e.g., Birch, 1964, JGR). Experimental data on the partitioning behavior of siderophile elements such as Ni and Co between liquid Fe and mantle minerals indicate that equilibration between core-forming metal and a silicate magma ocean likely occurred at lower-mantle pressures (e.g., Li and Agee, 1996 Nature). If core-mantle differentiation has occurred under such conditions, significant quantities of O or Si could have entered the core. At these conditions the nature of the dominant light element in the core will depend strongly on the oxygen fugacity at which equilibration occurred. High pressure experiments were carried out at 25 GPa and 2400-2950 K using a Kawai-type multi-anvil apparatus in order to investigate the partitioning of Si and O between liquid Fe and (Mg,Fe)SiO3 perovskite (Pv), silicate melt, and (Mg,Fe)O ferropericlace (Fp). Starting materials consisting of metallic Fe (+-Si) and olivine (Fo70-95) were contained in single-crystal MgO capsules. Over the oxygen fugacity range IW-0.5 to -3, the Si molar partition coefficient D* (= [Si]metal /[Si]silicate) between metal and Pv increases linearly with decreasing oxygen fugacity at a fixed given temperature. The partition coefficient between metal and silicate melt is of a similar magnitude but is less dependent on the oxygen fugacity. The obtained oxygen distribution coefficient Kd (= [Fe]metal[O]metal /[FeO]Fp) is in agreement with that determined in the Fe-Fp binary system (Asahara et al., 2007 EPSL) below the silicate liquidus temperature. In contrast, a correlation between the O partitioning and Si concentration in Fe is observed above 2700 K where liquid metal coexists with silicate melt + Fp. With an increasing concentration of Si in the liquid metal, O partitioning into Fp is strongly enhanced. Five atomic% Si in the metal reduces the metal-silicate O partition coefficient by about 1 order magnitude. Near the base of a deep magma ocean where pressures exceed 20 GPa, liquid metal could have coexisted with silicate melt, Pv, and Fp. Our results show that Si would readily partitioned into core-forming metal from both perovskite and silicate liquid at a relevant oxygen fugacity (e.g., IW-2). Simultaneously, the Si solubility would hinder the dissolution of O in the liquid metal. This implies that the presence of Si in liquid metal must be included in models of O partitioning.
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NASA Technical Reports Server (NTRS)
Murrell, M. T.; Burnett, D. S.
1986-01-01
Experimental partitioning studies are reported of K, U, and Th between silicate and FeFeS liquids designed to test the proposal that actinide partitioning into sulfide liquids is more important then K partitioning in the radioactive heating of planetary cores. For a basaltic liquid at 1450 C and 1.5 GPa, U partitioning into FeFeS liquids is five times greater than K partitioning. A typical value for the liquid partition coefficient for U from a granitic silicate liquid at one atmosphere at 1150 C and low fO2 is about 0.02; the coefficient for Th is similar. At low fO2 and higher temperature, experiments with basaltic liquids produce strong Ca and U partitioning into the sulfide liquid with U coefficient greater than one. The Th coefficient is less strongly affected.
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Interior of Mars from spacecraft and complementary data.
NASA Astrophysics Data System (ADS)
Dehant, Veronique
2015-04-01
Mars, as Earth, Venus and Mercury is a terrestrial planet having, in addition to the mantle and lithosphere, a core composed of an iron alloy. This core might be completely liquid, completely solid or may contain a solid part (the inner core) and a liquid part. The existence of a magnetic field around a planet is mainly explained by the presence of motions in the liquid part in the core. The absence of a magnetic field does not help in constraining the state of the core as it might be completely solid or completely liquid but the motion (convection) might not be sufficient to maintain it, or even contain a growing inner core inside a liquid core composed of iron or Nickel and a percentage of light element corresponding to the eutectic composition (no precipitation). The planet Mars is smaller than Earth. It has evolved differently. We know for the Earth that the core is liquid and that the inner core is forming by precipitation of iron. For Mars spacecraft observation of the gravity field and its time variation allow us to obtain the effect of mass repartition, and in particular those induced by the solid tides. These tidal deformation of the planet are larger for a planet with a liquid core than for a completely solid planet. Recent spacecraft orbiting around Mars (MGS, Mars Odyssey, MRO, Mars Express) have allowed to obtain the k2 tidal Love numbers. This measurement is rather at the limit of what the observation can tell us but seems to indicate that Mars has a liquid core. The absence of a present-day global magnetic field places Mars in the situation where the inner core is not yet forming or has reached the eutectic. Physical observation of the planet other than tides also allow us to obtain information about the interior of Mars: its rotation and orientation changes. Planetary rotation can be separated into the rotation speed around an axis and the orientation of this axis (or another axis of the planet) in space. Most of us know that the rotation of a boiled egg noticeably differs from that of a raw egg. This simple observation shows that information on the inside of an object can be obtained from its rotation. The same idea applies to the rotation of celestial bodies. Their rotation changes and orientation changes provide information on the interior. For Mars, as for the Earth, it is mainly the changes in the orientation that are important to characterize their interiors, the length-of-day variations being mostly related to atmospheric angular moment transfer to the solid planet. The orientation changes are called precession, the long-term change, and nutation, the periodic wiggly short-term changes that are the most interesting to obtain information about the core. Nutations have up to now only been unambiguously observed for the Earth, but the InSIGHT (Interior exploration using Seismic Investigations, Geodesy, and Heat Transport) NASA mission to be launched in 2016, will carry out an X-band transponder enabling us to do Doppler measurements on the motion of Mars with respect to Earth, and therewith to determine the nutations and the interior structure of Mars.
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In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles
Chu, Sheng-Hua; Karri, Surya; Ma, Yan-Bin; Feng, Dong-Fu; Li, Zhi-Qiang
2013-01-01
Background Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs. Methods In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model. Results Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. The number of γH2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. Conclusions These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe. PMID:23519742
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In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles.
Chu, Sheng-Hua; Karri, Surya; Ma, Yan-Bin; Feng, Dong-Fu; Li, Zhi-Qiang
2013-07-01
Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs. In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model. Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. The number of γH2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe.
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Inhibiting DNA-PK{sub CS} radiosensitizes human osteosarcoma cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.
Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK{sub CS}), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PK{sub CS} in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK{sub CS} inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PK{submore » CS} was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PK{sub CS} inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively radiosensitizes osteosarcoma cells. • Combining KU60648 with radiation increases G2/M accumulation and DNA damage.« less
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Magnetic properties and core electron binding energies of liquid water
NASA Astrophysics Data System (ADS)
Galamba, N.; Cabral, Benedito J. C.
2018-01-01
The magnetic properties and the core and inner valence electron binding energies of liquid water are investigated. The adopted methodology relies on the combination of molecular dynamics and electronic structure calculations. Born-Oppenheimer molecular dynamics with the Becke and Lee-Yang-Parr functionals for exchange and correlation, respectively, and includes an empirical correction (BLYP-D3) functional and classical molecular dynamics with the TIP4P/2005-F model were carried out. The Keal-Tozer functional was applied for predicting magnetic shielding and spin-spin coupling constants. Core and inner valence electron binding energies in liquid water were calculated with symmetry adapted cluster-configuration interaction. The relationship between the magnetic shielding constant σ(17O), the role played by the oxygen atom as a proton acceptor and donor, and the tetrahedral organisation of liquid water are investigated. The results indicate that the deshielding of the oxygen atom in water is very dependent on the order parameter (q) describing the tetrahedral organisation of the hydrogen bond network. The strong sensitivity of magnetic properties on changes of the electronic density in the nuclei environment is illustrated by a correlation between σ(17O) and the energy gap between the 1a1[O1s] (core) and the 2a1 (inner valence) orbitals of water. Although several studies discussed the eventual connection between magnetic properties and core electron binding energies, such a correlation could not be clearly established. Here, we demonstrate that for liquid water this correlation exists although involving the gap between electron binding energies of core and inner valence orbitals.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wolfe, T; Reynoso, F; Cho, J
2015-06-15
Purpose: To assess the potential to amplify radiosensitization of cancer cells targeted with gold nanoparticles by augmenting selective spectral components of X-ray beam. Methods: Human prostate cancer cells were treated for 24h with gold nanorods conjugated to goserelin acetate or pegylated, systematically washed and irradiated with 250 kVp X-rays (25mA, 0.25mm Cu- filter, 8x8cm{sup 2} field size, 50cm SSD) with or without an additional 0.25 mm Erbium (Er) filter. As demonstrated in a companion Monte Carlo study, Er-filter acted as an external target to feed Erbium K-shell X-ray fluorescence photons (∼50 keV) into the 250 kVp beam. After irradiation, wemore » performed measurements of clonogenic viability with doses between 0 -6Gy, irreparable DNA damage assay to measure double-strand breaks via γH2AX-foci staining, and production of stable reactive oxygen species (ROS). Results: The clonogenic assay for the group treated with conjugated nanoparticles showed radiosensitization enhancement factor (REF), calculated at the 10% survival fraction aisle, of (1.62±0.07) vs. (1.23±0.04) with/without the Er-filter in the 250 kVp beam, respectively. The group treated with pegylated nanoparticles, albeit retained in modest amounts within the cells, also showed statistically significant REF (1.13±0.09) when the Erbium filter was added to the beam. No significant radiosensitization was observed for other groups. Measurements of ROS levels showed increments of (1.9±0.2) vs. (1.4±0.1) for combined treatment with targeted nanoparticles and Er-filtered beam. γH2AX-foci showed 50% increase for the same treatment combination, confirming the enhanced radiosensitization in a consistent fashion. Conclusion: Our study demonstrates the feasibility of enhancing radiosensitization of cancer cells by combining actively targeted gold nanoparticles and modulating the X-ray spectrum in the desired energy range. The established technique will not only help develop strategies to maximize nanoparticle-mediated radiosensitization but also offer a convenient way to acquire unprecedented insights into the role of photon energy for the observed radiosensitization effects. Supported by DOD/PCRP grant W81XWH-12-1-0198.« less
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Gamma thermometer based reactor core liquid level detector
Burns, Thomas J.
1983-01-01
A system is provided which employs a modified gamma thermometer for determining the liquid coolant level within a nuclear reactor core. The gamma thermometer which normally is employed to monitor local core heat generation rate (reactor power), is modified by thermocouple junctions and leads to obtain an unambiguous indication of the presence or absence of coolant liquid at the gamma thermometer location. A signal processor generates a signal based on the thermometer surface heat transfer coefficient by comparing the signals from the thermocouples at the thermometer location. The generated signal is a direct indication of loss of coolant due to the change in surface heat transfer when coolant liquid drops below the thermometer location. The loss of coolant indication is independent of reactor power at the thermometer location. Further, the same thermometer may still be used for the normal power monitoring function.
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NASA Technical Reports Server (NTRS)
Go, B. M.; Righter, K.; Danielson, L.; Pando, K.
2015-01-01
Previous geochemical and geophysical experiments have proposed the presence of a small, metallic lunar core, but its composition is still being investigated. Knowledge of core composition can have a significant effect on understanding the thermal history of the Moon, the conditions surrounding the liquid-solid or liquid-liquid field, and siderophile element partitioning between mantle and core. However, experiments on complex bulk core compositions are very limited. One limitation comes from numerous studies that have only considered two or three element systems such as Fe-S or Fe-C, which do not supply a comprehensive understanding for complex systems such as Fe-Ni-S-Si-C. Recent geophysical data suggests the presence of up to 6% lighter elements. Reassessments of Apollo seismological analyses and samples have also shown the need to acquire more data for a broader range of pressures, temperatures, and compositions. This study considers a complex multi-element system (Fe-Ni-S-C) for a relevant pressure and temperature range to the Moon's core conditions.
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Two-Phase Dynamics Simulations of the Growth and Instability of Earth's Inner Core
NASA Astrophysics Data System (ADS)
Hernlund, J. W.; Jellinek, M.; Labrosse, S.
2008-12-01
When the center of Earth's core began to freeze from a homogeneous liquid 1-2 billion years ago, its constitution was very likely that of a mushy region. As this incipient inner core grew by further crystallization of the outer core, an increase in gravity force allowed for the solid grains to compress against one another, undergo viscous compaction, and begin to expel remnant fluid out of the inner core by percolation. Meanwhile, inside the inner core the residual fluid and solid remained in equilibrium, and any perturbations that resulted in upwelling of the deformable mush would also be accompanied by decompression melting. Upwelling and melting regions might then increase in liquid fraction, become less dense, and hence buoyant in a way that would propel them upward at a faster rate, setting up a runaway instability and partial Rayleigh-Taylor-like overturn of Earth's inner core. Structures inherited from this event possibly include the distinct innermost inner core posited by seismologists to exist at Earth's centermost 300-600 km. We use a new two-phase dynamics code to model this scenario in axi-symmetric geometry in order to understand whether and when such an instability occurred, what size the core will have been at the onset of instability, and the degree and style of deformation that would have accompanied this episode. We have found that the growth of instability competes with the rate of background melt percolation, such that the instability would only have occurred after the inner core reaches a critical size and expelled a certain amount of liquid from its interior. A linear stability analysis confirms that there is a critical Rayleigh number for the onset of instability at a given radius. The combined constraints show that the inner core is guaranteed to have undergone this kind of instability, at a time and strength governed solely by physical properties such as grain size, density differences between liquid and solid, and viscosities of the phases.
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Tao, Shiquan; Winstead, Christopher B.
2005-04-12
A monitor is provided for use in measuring the concentration of hexavalent chromium in a liquid, such as water. The monitor includes a sample cell, a light source, and a photodetector. The sample cell is in the form of a liquid-core waveguide, the sample cell defining an interior core and acting as a receiver for the liquid to be analyzed, the interior surface of the sample cell having a refractive index of less than 1.33. The light source is in communication with a first end of the sample cell for emitting radiation having a wavelength of about and between 350 to 390 nm into the interior core of the waveguide. The photodetector is in communication with a second end of the waveguide for measuring the absorption of the radiation emitted by the light source by the liquid in the sample cell. The monitor may also include a processor electronically coupled to the photodetector for receipt of an absorption signal to determine the concentration of hexavalent chromium in the liquid.
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Earth's Core-Mantle equilibrium and a heat sink at the Core Mantle Boundary
NASA Astrophysics Data System (ADS)
Alfe, D.; Pozzo, M.; Davies, C. J.; Gubbins, D.
2016-12-01
Chemical equilibrium between the two sides of the core mantle boundary (CMB) has longbeen debated. If the core is well mixed and in equilibrium with the inner coredisequilibrium at the CMB seems inevitable. Indeed, a number of experiments pointto a possible non-equilibrium configuration in which the core liquid iron mixture wouldbe undersaturated in oxygen. As discussed by several authors, this chemical imbalancecould result in the formation of an oxygen rich layer at the top of the core, and astratification, which could explain a seismic anomaly claimed by some authors.Here we have revisited the core-mantle equilibrium by calculating the chemical potentialof FeO in both liquid iron mixtures and solid Periclase at CMB conditions, usingfirst principles methods based on quantum mechanics and standard statistical mechanics.We find that FeO is favoured in the liquid mixture, with an equilibrium O concentrationthat is much larger than that of the bulk core. In addition, we find that the heat ofreaction of the FeO dissolution form the mantle to the core is positive, making thereaction endothermic, and therefore providing a heat sink at the top of the core.The power lost in the heat sink depends on the rate of FeO dissolution, and we discussa scenario which could result in a heat sink of several TW. This sink would absorbsome of the heat conducted along the core adiabat and reduce the CMB heat flux.
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NASA Astrophysics Data System (ADS)
Jin, H.; Kozdras, M. S.; Amirkhiz, B. Shalchi; Winkler, S. L.
2018-05-01
The liquid-solid interaction during brazing at 592 °C to 605 °C and its effects on mechanical properties were investigated in a series of Al-Si/Al-Mn-Cu-Mg brazing sheets with different Mg contents. Depending on the Mg level in core alloy and the brazing temperature, critical changes of local chemistry and microstructure related to the liquid-solid interaction occur, including solid-state diffusion, uniform clad-core interface migration, and grain boundary penetration (GBP). When the Mg in core alloy is below 1 wt pct, the interaction is limited and the formation of a dense precipitation band due to solid-state diffusion of Si from the clad to the core is dominant. As the Mg exceeds 1 wt pct, very extensive interaction occurs resulting in clad-core interface migration and GBP of Si into the core, both involving local melting and re-solidification of the core alloy. Whenever Si from the clad encounters Mg in the core due to the interaction, Mg2Si precipitates are formed leading to significant improvement of strength. However, the interface migration and GBP drastically reduce the ductility, due to the segregation of coarse secondary phase particles along the newly formed grain boundaries.
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NASA Astrophysics Data System (ADS)
Jin, H.; Kozdras, M. S.; Amirkhiz, B. Shalchi; Winkler, S. L.
2018-07-01
The liquid-solid interaction during brazing at 592 °C to 605 °C and its effects on mechanical properties were investigated in a series of Al-Si/Al-Mn-Cu-Mg brazing sheets with different Mg contents. Depending on the Mg level in core alloy and the brazing temperature, critical changes of local chemistry and microstructure related to the liquid-solid interaction occur, including solid-state diffusion, uniform clad-core interface migration, and grain boundary penetration (GBP). When the Mg in core alloy is below 1 wt pct, the interaction is limited and the formation of a dense precipitation band due to solid-state diffusion of Si from the clad to the core is dominant. As the Mg exceeds 1 wt pct, very extensive interaction occurs resulting in clad-core interface migration and GBP of Si into the core, both involving local melting and re-solidification of the core alloy. Whenever Si from the clad encounters Mg in the core due to the interaction, Mg2Si precipitates are formed leading to significant improvement of strength. However, the interface migration and GBP drastically reduce the ductility, due to the segregation of coarse secondary phase particles along the newly formed grain boundaries.
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Lee, Sang Seok; Seo, Hyeon Jin; Kim, Yun Ho; Kim, Shin-Hyun
2017-06-01
Photonic microcapsules with onion-like topology are microfluidically designed to have cholesteric liquid crystals with opposite handedness in their core and shell. The microcapsules exhibit structural colors caused by dual photonic bandgaps, resulting in a rich variety of color on the optical palette. Moreover, the microcapsules can switch the colors from either core or shell depending on the selection of light-handedness. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Orth, M; Unger, K; Schoetz, U; Belka, C; Lauber, K
2018-01-04
Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated radiosensitization of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression. This distinct mitotic phenotype was interlinked with Paclitaxel-mediated radiosensitization via overexpression of mitotic Aurora kinase A (AURKA) and its cofactor TPX2 whose knockdown rescued the bipolar mode of cell division and largely attenuated the radiosensitizing effects of Paclitaxel. In the cancer genome atlas (TCGA) lung adenocarcinoma cohort, high expression levels of AURKA and TPX2 were associated with specifically improved overall survival upon taxane-based radiochemotherapy, but not in case of non-taxane-based radiochemotherapy, chemo- or radiotherapy only. Thus, our data provide insights into Paclitaxel-mediated radiosensitization on a mechanistic and molecular level and identify AURKA and TPX2 as the first potential mechanism-based, predictive markers of taxane-based radiochemotherapy.
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Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks.
Wang, Huichen; Boecker, Wilfried; Wang, Hongyan; Wang, Xiang; Guan, Jun; Thompson, Larry H; Nickoloff, Jac A; Iliakis, George
2004-01-22
We recently reported that two Chinese hamster mutants deficient in the RAD51 paralogs XRCC2 and XRCC3 show reduced radiosensitization after treatment with caffeine, thus implicating homology-directed repair (HDR) of DNA double-strand breaks (DSBs) in the mechanism of caffeine radiosensitization. Here, we investigate directly the effect of caffeine on HDR initiated by DSBs induced by a rare cutting endonuclease (I-SceI) into one of two direct DNA repeats. The results demonstrate a strong inhibition by caffeine of HDR in wild-type cells, and a substantial reduction of this effect in HDR-deficient XRCC3 mutant cells. Inhibition of HDR and cell radiosensitization to killing shows similar dependence on caffeine concentration suggesting a cause-effect relationship between these effects. UCN-01, a kinase inhibitor that effectively abrogates checkpoint activation in irradiated cells, has only a small effect on HDR, indicating that similar to radiosensitization, inhibition of checkpoint signaling is not sufficient for HDR inhibition. Recombination events occurring during treatment with caffeine are characterized by rearrangements reminiscent to those previously reported for the XRCC3 mutant, and immunofluorescence microscopy demonstrates significantly reduced formation of IR-specific RAD51 foci after caffeine treatment. In summary, our results identify inhibition of HDR as a significant contributor to caffeine radiosensitization.
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Chloronitroimidazoles as radiosensitizers of hypoxic cells in vitro.
Wideł, M; Watras, J; Suwiński, J; Salwińska, E
1987-01-01
Some results of the first more complex studies in vitro on radio-sensitizing efficiency, cytotoxicity and reactivity with blood-thiols of a series of 4- or 5-nitroimidazoles substituted in the 5, 4 or 2 position with chlorine are presented. The derivatives of 4-nitroimidazole substituted in 5 position ("ortho" position) with Cl show higher radiosensitizing efficiency than one may expect from their reduction potential, E1/2. At the same time they are extremely toxic, especially for aerobic cells. It is considered that high biological activity of ortho-substituted 4-nitroimidazoles is connected with their considerable chemical reactivity towards thiols and suppression of those natural protective compounds in the cells. The corresponding 5-nitro isomers are about tenfold weaker sensitizers, and simultaneously much less cytotoxic, either in aerobic or in hypoxic conditions. The chloro-4(5)-nitroimidazoles nonsubstituted at N-1 and ionizable in aqueous solution are relatively weaker at the same time less toxic radiosensitizers. It is evaluated that potential application in radiotherapy may have those chloronitroimidazoles which show low aerobic cytotoxicity, moderate radiosensitizing ability and no reactivity towards thiols. On the basis of the study in vitro, we have selected such a compound: 1-methyl-2-chloro-4-nitroimidazole (P13) for screening in vivo.
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Surface Interaction of Bent-Core Liquid Crystals "Slipping on a Banana Peel"
NASA Astrophysics Data System (ADS)
Iglesias Gonzalez, Wilder G.
The main emphasis and focus of this talk revolves around liquid crystalline molecules with frustrated symmetry, molecules with a kink in the core resembling the shape of a banana. These novel materials are not only suitable and interesting for the common liquid crystal display field as fast switching candidates, but for a whole wide range of potential applications, such as: power generation, microscale actuators, optical storage devices, to name a few. Understanding surface interactions of these mesogens is a key factor in controlling and unveiling the vast potential capabilities of such liquid crystals.
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On the Composition and Temperature of the Terrestrial Planetary Core
NASA Astrophysics Data System (ADS)
Fei, Yingwei
2013-06-01
The existence of liquid cores of terrestrial planets such as the Earth, Mar, and Mercury has been supported by various observation. The liquid state of the core provides a unique opportunity for us to estimate the temperature of the core if we know the melting temperature of the core materials at core pressure. Dynamic compression by shock wave, laser-heating in diamond-anvil cell, and resistance-heating in the multi-anvil device can melt core materials over a wide pressure range. There have been significant advances in both dynamic and static experimental techniques and characterization tool. In this tal, I will review some of the recent advances and results relevant to the composition and thermal state of the terrestrial core. I will also present new development to analyze the quenched samples recovered from laser-heating diamond-anvil cell experiments using combination of focused ion beam milling, high-resolution SEM imaging, and quantitative chemical analysi. With precision milling of the laser-heating spo, the melting point and element partitioning between solid and liquid can be precisely determined. It is also possible to re-construct 3D image of the laser-heating spot at multi-megabar pressures to better constrain melting point and understanding melting process. The new techniques allow us to extend precise measurements of melting relations to core pressures, providing better constraint on the temperature of the cor. The research is supported by NASA and NSF grants.
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NASA Astrophysics Data System (ADS)
Brazhkin, Vadim V.; Lyapin, A. G.
2000-05-01
Experimental data on and theoretical models for the viscosity of various types of liquids and melts under pressure are reviewed. Experimentally, the least studied melts are those of metals, whose viscosity is considered to be virtually constant along the melting curve. The authors' new approach to the viscosity of melts involves the measurement of the grain size in solidified samples. Measurements on liquid metals at pressures up to 10 GPa using this method show, contrary to the empirical approach, that the melt viscosity grows considerably along the melting curves. Based on the experimental data and on the critical analysis of current theories, a hypothesis of a universal viscosity behavior is introduced for liquids under pressure. Extrapolating the liquid iron results to the pressures and temperatures at the Earth's core reveals that the Earth's outer core is a very viscous melt with viscosity values ranging from 102 Pa s to 1011 Pa s depending on the depth. The Earth's inner core is presumably an ultraviscous (>1011 Pa s) glass-like liquid — in disagreement with the current idea of a crystalline inner core. The notion of the highly viscous interior of celestial bodies sheds light on many mysteries of planetary geophysics and astronomy. From the analysis of the pressure variation of the melting and glass-transition temperatures, an entirely new concept of a stable metallic vitreous state arises, calling for further experimental and theoretical study.
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Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.
Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.« less
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Wahba, Amy; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J
2018-06-04
Analysis of the radiation-induced translatome of glioblastoma stem-like cells (GSCs) identified an interacting network in which XPO1 serves as a major hub protein. To determine whether this nuclear export protein provides a target for radiosensitization, we defined the effects of the clinically relevant XPO1 inhibitor Selinexor on the radiosensitivity of glioblastoma cells. As determined by clonogenic survival analysis, Selinexor enhanced the radiosensitivity of GSCs but not normal fibroblast cell lines. Based on γH2AX foci and neutral comet analyses, Selinexor inhibited the repair of radiation-induced DNA double strand breaks in GSCs suggesting that the Selinexor-induced radiosensitization is mediated by an inhibition of DNA repair. Consistent with a role for XPO1 in the nuclear to cytoplasm export of rRNA, Selinexor reduced 5S and 18S rRNA nuclear export in GSCs, which was accompanied by a decrease in gene translation efficiency, as determined from polysome profiles, as well as in protein synthesis. In contrast, rRNA nuclear export and protein synthesis were not reduced in normal cells treated with Selinexor. Orthotopic xenografts initiated from a GSC line were then used to define the in vivo response to Selinexor and radiation. Treatment of mice bearing orthotopic xenografts with Selinexor decreased tumor translational efficiency as determined from polysome profiles. Although Selinexor treatment alone had no effect on the survival of mice with brain tumors, it significantly enhanced the radiation-induced prolongation of survival. These results indicate that Selinexor enhances the radiosensitivity of glioblastoma cells and suggest that this effect involves a global inhibition of gene translation. Copyright ©2018, American Association for Cancer Research.
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Inkoom, Stephen; Raissaki, Maria; Perisinakis, Kostas; Maris, Thomas G; Damilakis, John
2015-12-01
The aim of this study was to determine the location of radiosensitive organs in the interior of four pediatric anthropomorphic phantoms for dosimetric purposes. Four pediatric anthropomorphic phantoms representing the average individual as newborn, 1-year-old, 5-year-old and 10-year-old child underwent head, thorax and abdomen CT scans. CT and MRI scans of all children aged 0-16 years performed during a 5-year-period in our hospital were reviewed, and 503 were found to be eligible for normal anatomy. Anterior-posterior and lateral dimensions of twelve of the above children closely matched that of the phantoms' head, thoracic and abdominal region in each four phantoms. The mid-sagittal and mid-coronal planes were drawn on selected matching axial images of patients and phantoms. Multiple points outlining large radiosensitive organs in patient images were identified at each slice level and their orthogonal distances from the mid-sagittal and mid-coronal planes were measured. In small organs, the coordinates of organs' centers were similarly determined. The outlines and centers of all radiosensitive organs were reproduced using the coordinates of each organ on corresponding phantoms' transverse images. The locations of the following radiosensitive organs in the interior of the four phantoms was determined: brain, eye lenses, salivary glands, thyroid, lungs, heart, thymus, esophagus, breasts, adrenals, liver, spleen, kidneys, stomach, gallbladder, small bowel, pancreas, colon, ovaries, bladder, prostate, uterus and rectum. The production of charts of radiosensitive organs inside pediatric anthropomorphic phantoms was feasible and may provide users reliable data for positioning of dosimeters during direct organ dose measurements. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Matthews, Q; Lum, JJ; Isabelle, M
Purpose: To use label-free Raman spectroscopy (RS) for early treatment monitoring of tumour cell radioresistance. Methods: Three human tumour cell lines, two radioresistant (H460, SF{sub 2} = 0.57 and MCF7, SF{sub 2} = 0.70) and one radiosensitive (LNCaP, SF{sub 2} = 0.36), were irradiated with single fractions of 2, 4, 6, 8 or 10 Gy. In additional experiments, H460 and MCF7 cells were irradiated under co-treatment with the anti-diabetic drug metformin, a known radiosensitizing agent. Treated and control cultures were analyzed with RS daily for 3 days post-treatment. Single-cell Raman spectra were acquired from 20 live cells per sample, andmore » experiments were repeated in triplicate. The combined data sets were analyzed with principal component analysis using standard algorithms. Cells from each culture were also subjected to standard assays for viability, proliferation, cell cycle, and radiation clonogenic survival. Results: The radioresistant cells (H460, MCF7) exhibited a RS molecular radiation response signature, detectable as early as 1 day post-treatment, of which radiation-induced glycogen synthesis is a significant contributor. The radiosensitive cells (LNCaP) exhibited negligible glycogen synthesis. Co-treatment with metformin in MCF7 cells blocked glycogen synthesis, reduced viability and proliferation, and increased radiosensitivity. Conversely, metformin co-treatment in H460 cells did not produce these same effects; importantly, both radiation-induced synthesis of glycogen and radiosensitivity were unaffected. Conclusions: Label-free RS can detect early glycogen synthesis post-irradiation, a previously undocumented metabolic mechanism associated with tumour cell radioresistance that can be targeted to increase radiosensitivity. RS monitoring of intratumoral glycogen may provide new opportunities for personalized combined modality radiotherapy treatments.« less
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Lu, Hongzhi; He, Yu; Lin, Lin; Qi, Zhengqin; Ma, Li; Li, Li; Su, Ying
2016-02-01
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA playing oncogenic role in several cancers, including cervical cancer. However, its role in radiosensitivity of cervical cancer is not yet well understood. This study explored the role of MALAT1 in radiosensitivity of high-risk human papillomavirus (HR-HPV)-positive cervical cancer and whether there is a ceRNA mechanism which participated in its regulation over radiosensitivity. Based on tissue samples from 50 cervical cancer cases and 25 healthy controls, we found MALAT1 expression was significantly higher in radioresistant than in radiosensitive cancer cases. In addition, MALAT1 and miR-145 expression inversely changed in response to irradiation in HR-HPV+ cervical cancer cells. By using clonogenic assay and flow cytometry analysis of cell cycle distribution and apoptosis, we found CaSki and Hela cells with knockdown of MALAT1 had significantly lower colony formation, higher ratio of G2/M phase block and higher ratio of cell apoptosis. By performing RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay, we confirmed that miR-145 and MALAT1 were in the same Ago2 complex and there was a reciprocal repression between them. Then, we explored the function of MALAT1-miR-145 in radiosensitivity of cervical cancers cells and demonstrated that si-MALAT1 and miR-145 had some level of synergic effect in reducing cancer cell colony formation, cell cycle regulation, and inducing apoptosis. These findings provide an important clue about microRNA-lncRNA interaction in the mechanism of radioresistance of cervical cancer.
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DNA-Dependent Protein Kinase As Molecular Target for Radiosensitization of Neuroblastoma Cells.
Dolman, M Emmy M; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N; Molenaar, Jan J
2015-01-01
Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to radiosensitize neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for radiosensitization of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. Radiosensitizing effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically radiosensitized other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma radiosensitization.
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Masunaga, S; Sakurai, Y; Tanaka, H; Hirayama, R; Matsumoto, Y; Uzawa, A; Suzuki, M; Kondo, N; Narabayashi, M; Maruhashi, A; Ono, K
2013-01-01
Objective To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). Methods EL4 tumour-bearing C57BL/J mice received 5-bromo-29-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with c-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a 10B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. Results Following c-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a 10B-carrier, especially L-para-boronophenylalanine-10B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. Conclusion The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the 10B-carrier used in the BNCR. Advances in knowledge The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control. PMID:23255546
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DNA-Dependent Protein Kinase As Molecular Target for Radiosensitization of Neuroblastoma Cells
Dolman, M. Emmy M.; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.
2015-01-01
Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to radiosensitize neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for radiosensitization of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. Radiosensitizing effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically radiosensitized other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma radiosensitization. PMID:26716839
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Enhancement of P53-Mutant Human Colorectal Cancer Cells Radiosensitivity by Flavonoid Fisetin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen Wenshu; Lee Yijang; Yu Yichu
Purpose: The aim of this study was to investigate whether fisetin is a potential radiosensitizer for human colorectal cancer cells, which are relatively resistant to radiotherapy. Methods and Materials: Cell survival was examined by clonogenic survival assay, and DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The effects of treatments on cell cycle distribution and apoptosis were examined by flow cytometry. Western blot analysis was performed to ascertain the protein levels of {gamma}-H2AX, phospho-Chk2, active caspase-3, PARP cleavage, phospho-p38, phospho-AKT, and phospho-ERK1/2. Results: Fisetin pretreatment enhanced the radiosensitivity of p53-mutant HT-29 human colorectal cancer cellsmore » but not human keratocyte HaCaT cells; it also prolonged radiation-induced G{sub 2}/M arrest, enhanced radiation-induced cell growth arrest in HT-29 cells, and suppressed radiation-induced phospho-H2AX (Ser-139) and phospho-Chk2 (Thr-68) in p53-mutant HT-29 cells. Pretreatment with fisetin enhanced radiation-induced caspase-dependent apoptosis in HT-29 cells. Fisetin pretreatment augmented radiation-induced phosphorylation of p38 mitogen-activated protein kinase, which is involved in caspase-mediated apoptosis, and SB202190 significantly reduced apoptosis and radiosensitivity in fisetin-pretreated HT-29 cells. By contrast, both phospho-AKT and phospho-ERK1/2, which are involved in cell proliferation and antiapoptotic pathways, were suppressed after irradiation combined with fisetin pretreatment. Conclusions: To our knowledge, this study is the first to provide evidence that fisetin exerts a radiosensitizing effect in p53-mutant HT-29 cells. Fisetin could potentially be developed as a novel radiosensitizer against radioresistant human cancer cells.« less
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Masunaga, S; Sakurai, Y; Tanaka, H; Hirayama, R; Matsumoto, Y; Uzawa, A; Suzuki, M; Kondo, N; Narabayashi, M; Maruhashi, A; Ono, K
2013-01-01
To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). EL4 tumour-bearing C57BL/J mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a (10)B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a (10)B-carrier, especially L-para-boronophenylalanine-(10)B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the (10)B-carrier used in the BNCR. The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.
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Gursoy-Yuzugullu, Ozge; Carman, Chelsea; Serafim, Rodolfo Bortolozo; Myronakis, Marios; Valente, Valeria; Price, Brendan D
2017-04-11
Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance. Here, we demonstrate that inhibitors of the H4K20 methyltransferase SETD8 (UNC-0379) and the H3K9 methyltransferase G9a (BIX-01294) are effective radiosensitizers of human glioma cells. UNC-0379 blocked H4K20 methylation and reduced recruitment of the 53BP1 protein to DSBs, although this loss of 53BP1 caused only limited changes in radiosensitivity. In contrast, loss of H3K9 methylation through G9a inhibition with BIX-01294 increased radiosensitivity of a panel of glioma cells (SER2Gy range: 1.5 - 2.9). Further, loss of H3K9 methylation reduced DSB signaling dependent on H3K9, including reduced activation of the Tip60 acetyltransferase, loss of ATM signaling and reduced phosphorylation of the KAP-1 repressor. In addition, BIX-0194 inhibited DSB repair through both the homologous recombination and nonhomologous end-joining pathways. Inhibition of G9a and loss of H3K9 methylation is therefore an effective approach for increasing radiosensitivity of glioma cells. These results suggest that combining inhibitors of histone methyltransferases which are critical for DSB repair with radiation therapy may provide a new therapeutic route for sensitizing gliomas and other tumors to radiation therapy.
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Ference, Edward W.; Houtman, John L.; Waldby, Robert N.
1977-01-01
A nuclear reactor, particularly a liquid-metal breeder reactor whose upper internals include provision for channeling the liquid metal flowing from the core-component assemblies to the outlet plenum in vertical paths in direction generally along the direction of the respective assemblies. The metal is channeled by chimneys, each secured to, and extending from, a grid through whose openings the metal emitted by a plurality of core-component assemblies encompassed by the grid flows. To reduce the stresses resulting from structural interaction, or the transmissive of thermal strains due to large temperature differences in the liquid metal emitted from neighboring core-component assemblies, throughout the chimneys and the other components of the upper internals, the grids and the chimneys are supported from the heat plate and the core barrel by support columns (double portal support) which are secured to the head plate at the top and to a member, which supports the grids and is keyed to the core barrel, at the bottom. In addition to being restrained from lateral flow by the chimneys, the liquid metal is also restrained from flowing laterally by a peripheral seal around the top of the core. This seal limits the flow rate of liquid metal, which may be sharply cooled during a scram, to the outlet nozzles. The chimneys and the grids are formed of a highly-refractory, high corrosion-resistant nickel-chromium-iron alloy which can withstand the stresses produced by temperature differences in the liquid metal. The chimneys are supported by pairs of plates, each pair held together by hollow stubs coaxial with, and encircling, the chimneys. The plates and stubs are a welded structure but, in the interest of economy, are composed of stainless steel which is not weld compatible with the refractory metal. The chimneys and stubs are secured together by shells of another nickel-chromium-iron alloy which is weld compatible with, and is welded to, the stubs and has about the same coefficient of expansion as the highly-refractory, high corrosion-resistant alloy.
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Stretchable inductor with liquid magnetic core
NASA Astrophysics Data System (ADS)
Lazarus, N.; Meyer, C. D.
2016-03-01
Adding magnetic materials is a well-established method for improving performance of inductors. However, traditional magnetic cores are rigid and poorly suited for the emerging field of stretchable electronics, where highly deformable inductors are used to wirelessly couple power and data signals. In this work, stretchable inductors are demonstrated based on the use of ferrofluids, magnetic liquids based on distributed magnetic particles, to create a compliant magnetic core. Using a silicone molding technique to create multi-layer fluidic channels, a liquid metal solenoid is fabricated around a ferrofluid channel. An analytical model is developed for the effects of mechanical strain, followed by experimental verification using two different ferrofluids with different permeabilities. Adding ferrofluid was found to increase the unstrained inductance by up to 280% relative to a similar inductor with a non-magnetic silicone core, while retaining the ability to survive uniaxial strains up to 100%.
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The past, present, and future of hockey-stick-shaped liquid crystals
NASA Astrophysics Data System (ADS)
Choi, E.-Joon
2014-02-01
Recently, the liquid crystalline materials with a bent-core mesogen have attracted attentions because their interesting properties such as polarity and biaxiality of the mesophase. There are several types of bent-core mesogenic structures have been reported, for instance, banana-shaped, V-shaped molecules, boomerang-shaped, hockey stick-shaped, and Yshaped molecules. In this study, the liquid crystals and the reactive mesogens with the hockey-stick shaped mesogens will be described concerning with the structure-property relationship.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Izvekov, Sergei, E-mail: sergiy.izvyekov.civ@mail.mil; Rice, Betsy M.
2015-12-28
A core-softening of the effective interaction between oxygen atoms in water and silica systems and its role in developing anomalous thermodynamic, transport, and structural properties have been extensively debated. For silica, the progress with addressing these issues has been hampered by a lack of effective interaction models with explicit core-softening. In this work, we present an extension of a two-body soft-core interatomic force field for silica recently reported by us [S. Izvekov and B. M. Rice, J. Chem. Phys. 136(13), 134508 (2012)] to include three-body forces. Similar to two-body interaction terms, the three-body terms are derived using parameter-free force-matching ofmore » the interactions from ab initio MD simulations of liquid silica. The derived shape of the O–Si–O three-body potential term affirms the existence of repulsion softening between oxygen atoms at short separations. The new model shows a good performance in simulating liquid, amorphous, and crystalline silica. By comparing the soft-core model and a similar model with the soft-core suppressed, we demonstrate that the topology reorganization within the local tetrahedral network and the O–O core-softening are two competitive mechanisms responsible for anomalous thermodynamic and kinetic behaviors observed in liquid and amorphous silica. The studied anomalies include the temperature of density maximum locus and anomalous diffusivity in liquid silica, and irreversible densification of amorphous silica. We show that the O–O core-softened interaction enhances the observed anomalies primarily through two mechanisms: facilitating the defect driven structural rearrangements of the silica tetrahedral network and modifying the tetrahedral ordering induced interactions toward multiple characteristic scales, the feature which underlies the thermodynamic anomalies.« less
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Experimental constraints on the sulfur content in the Earth's core
NASA Astrophysics Data System (ADS)
Fei, Y.; Huang, H.; Leng, C.; Hu, X.; Wang, Q.
2015-12-01
Any core formation models would lead to the incorporation of sulfur (S) into the Earth's core, based on the cosmochemical/geochemical constraints, sulfur's chemical affinity for iron (Fe), and low eutectic melting temperature in the Fe-FeS system. Preferential partitioning of S into the melt also provides petrologic constraint on the density difference between the liquid outer and solid inner cores. Therefore, the center issue is to constrain the amount of sulfur in the core. Geochemical constraints usually place 2-4 wt.% S in the core after accounting for its volatility, whereas more S is allowed in models based on mineral physics data. Here we re-examine the constraints on the S content in the core by both petrologic and mineral physics data. We have measured S partitioning between solid and liquid iron in the multi-anvil apparatus and the laser-heated diamond anvil cell, evaluating the effect of pressure on melting temperature and partition coefficient. In addition, we have conducted shockwave experiments on Fe-11.8wt%S using a two-stage light gas gun up to 211 GPa. The new shockwave experiments yield Hugoniot densities and the longitudinal sound velocities. The measurements provide the longitudinal sound velocity before melting and the bulk sound velocity of liquid. The measured sound velocities clearly show melting of the Fe-FeS mix with 11.8wt%S at a pressure between 111 and 129 GPa. The sound velocities at pressures above 129GPa represent the bulk sound velocities of Fe-11.8wt%S liquid. The combined data set including density, sound velocity, melting temperature, and S partitioning places a tight constraint on the required sulfur partition coefficient to produce the density and velocity jumps and the bulk sulfur content in the core.
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Presumption of large-scale heterogeneity at the top of the outer core basal layer
NASA Astrophysics Data System (ADS)
Souriau, Annie
2015-04-01
A layer of reduced P-velocity gradient with thickness of about 100-200 km has been identified at the base of the liquid core from seismological methods. It has been interpreted as a dense layer resulting from partial re-melting of the inner core, which is depleted in light elements with respect to the liquid core during freezing. In an attempt to specify where freezing and re-melting occur, the structure of this basal layer is investigated with the seismological core phase PKPbc which has its turning point in the lower third of the outer core. The large PKPbc data set of the EHB catalog distributed by the International Seismological Centre is analyzed. In order to compensate for the uneven distribution of the data and to minimize the influence of mantle heterogeneities, the travel time anomalies are binned inside equal area and equal azimuth sectors sampling the base of the liquid core at different depths. Most of the observed variations in the binned travel time residuals are not significant according to their confidence level. The only features which could be significant are a large patch with a velocity increase of about 0.5% located at the top of the basal layer beneath the eastern hemisphere, and the complementary velocity decrease beneath the western hemisphere and the South pole. This observation suggests that some freezing or re-melting processes occur at the top of the basal layer with a hemispherical dissymmetry. If confirmed, it may give strong constraints on the fate of the light elements during the freezing and re-melting process and on their interaction with the basal layer and the overlying liquid core.
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Szulfer, Jarosław; Plenis, Alina; Bączek, Tomasz
2014-06-13
This paper focuses on the application of a column classification system based on the Katholieke Universiteit Leuven for the characterization of physicochemical properties of core-shell and ultra-high performance liquid chromatographic stationary phases, followed by the verification of the reliability of the obtained column classification in pharmaceutical practice. In the study, 7 stationary phases produced in core-shell technology and 18 ultra-high performance liquid chromatographic columns were chromatographically tested, and ranking lists were built on the FKUL-values calculated against two selected reference columns. In the column performance test, an analysis of alfuzosin in the presence of related substances was carried out using the brands of the stationary phases with the highest ranking positions. Next, a system suitability test as described by the European Pharmacopoeia monograph was performed. Moreover, a study was also performed to achieve a purposeful shortening of the analysis time of the compounds of interest using the selected stationary phases. Finally, it was checked whether methods using core-shell and ultra-high performance liquid chromatographic columns can be an interesting alternative to the high-performance liquid chromatographic method for the analysis of alfuzosin in pharmaceutical practice. Copyright © 2014 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Cerantola, V.; Walte, N. P.; Rubie, D. C.
2015-05-01
Deformation-assisted segregation of metallic and sulphidic liquid from a solid peridotitic matrix is a process that may contribute to the early differentiation of small planetesimals into a metallic core and a silicate mantle. Here we present results of an experimental study using a simplified system consisting of a polycrystalline Fo90-olivine matrix containing a small percentage of iron sulphide and a synthetic primitive MORB melt, in order to investigate whether the silicate melt enhances the interconnection and segregation of FeS liquid under deformation conditions at varying strain rates. The experiments have been performed at 2 GPa, 1450 °C and strain rates between 1 ×10-3s-1 to 1 ×10-5s-1. Our results show that the presence of silicate melt actually hinders the migration and segregation of sulphide liquid by reducing its interconnectivity. At low to moderate strain rates the sulphide liquid pockets preserved a roundish shape, showing the liquid behavior is governed mainly by surface tension rather than by differential stress. Even at the highest strain rates, insignificant FeS segregation and interconnection were observed. On the other hand the basaltic melt was very mobile during deformation, accommodating part of the strain, which led to its segregation from the matrix at high bulk strains leaving the sulphide liquid stranded in the olivine matrix. Hence, we conclude that deformation-induced percolation of sulphide liquid does not contribute to the formation of planetary cores after the silicate solidus is overstepped. A possible early deformation enhanced core-mantle differentiation after overstepping the Fe-S solidus is not possible between the initial formation of silicate melt and the formation of a widespread magma ocean.
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Liquid Iron Alloys with Hydrogen at Outer Core Conditions by First Principles
NASA Astrophysics Data System (ADS)
Umemoto, K.; Hirose, K.
2015-12-01
Since the density of the outer core deduced from seismic data is about 10% lower than that of pure iron at core pressures and temperatures (P-T), it is widely believed that the outer core includes one or more light elements. Although intensive experimental and theoretical studies have been performed so far, the light element in the core has not yet been identified. Comparison of the density and sound velocity of liquid iron alloys with observations, such as the PREM, is a promising way to determine the species and quantity of light alloying component(s) in the outer core. Here we report the results of a first-principles molecular dynamics study on liquid iron alloyed with hydrogen, one of candidates of the light elements. Hydrogen had been much less studied than other candidates. However, hydrogen has been known to reduce the melting temperature of Fe-H solid [1]. Furthermore, very recently, Nomura et al. argued that the outer core may include 24 at.% H in order to be molten under relatively low temperature (< 3600 K) [2]. Since then hydrogen has attracted strong interests. We clarify the effects of hydrogen on density and sound velocity of liquid iron alloys under outer core P-T conditions. It is shown that ~1 wt% hydrogen can reproduce PREM density and sound velocity simultaneously very well. In addition, we show the presence of hydrogen rather reduces Gruneisen parameters. It indicates that, if hydrogen exists in the outer core, temperature profile of the outer core could be changed considerably from one estimated so far. [1] Sakamaki, K., E. Takahashi, Y. Nakajima, Y. Nishihara, K. Funakoshi, T. Suzuki, and Y. Fukai, Phys. Earth Planet. Inter., 174, 192-201 (2009). [2] Nomura, R., K. Hirose, K. Uesugi, Y. Ohishi, A. Tsuchiyama, A. Miyake, and Y. Ueno, Science 31, 522-525 (2014).
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NASA Astrophysics Data System (ADS)
Ozawa, H.; Hirose, K.
2010-12-01
Element partitioning between molten iron and mantle minerals was investigated to 146 GPa by a combination of laser-heated diamond-anvil cell and analytical transmission electron microscope. The chemical compositions of co-existing quenched molten iron and (Mg,Fe)SiO3 perovskite/ferropericlase were determined quantitatively with energy-dispersive X-ray spectrometry and electron energy loss spectroscopy. The results demonstrate that the oxygen solubility in liquid iron co-existing with ferropericlase decreases with pressure to 38 GPa and, whereas the pressure effect is small at higher pressures. It was also revealed that the quenched liquid iron in contact with perovskite contained substantial amounts of oxygen and silicon at the core-mantle boundary (CMB) pressure. The chemical equilibrium between perovskite, ferropericlase, and molten iron at the P-T conditions of the CMB was calculated in Mg-Fe-Si-O system from these experimental results. Note that perovskite is a predominant phase instead of post-perovskite above 3500 K at the CMB pressure. We found that molten iron should include oxygen and silicon more than required to account for the core density deficit of below 10% when co-existing with both perovskite and ferropericlase at the CMB. This suggests that the bulk outer core liquid with <10% density deficit is not in direct contact with the mantle. Dissolutions of light elements from the mantle can produce a gravitationally stratified liquid layer at the topmost outer core, which can be responsible for the low-P wave velocity layer observed there. Such layer physically separates the mantle from the bulk outer core liquid, hindering the chemical reaction between them.
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NASA Astrophysics Data System (ADS)
Yu, T.; Long, H.; Young, C.; Wang, L.; Chen, J.
2005-12-01
From previous experimental and theoretical studies, sulfur has been considered one of the possible light elements in the core that might be responsible for the large density deficit when compared with the theoretical pure Fe core (Ganapathy and Anders, 1974; Ahrens and Jeanloz, 1987). Therefore, understanding the physical properties of liquid FeS will help us reveal the details of the Earth?|s core. This study focused on the liquid state of sulfur in iron due to sulfur?|s lack of amount in the mantle; easiness to alloy with iron; and the predicted 5 wt% ~10 wt% amount of this light element in the core (Ahrens, 1979; Sherman, 1997). Modern development of the multi-anvil high pressure apparatus limits the pressure range of the experiments (<30 GPa). It is somewhat low if comparing with the outer core pressure condition. Therefore, extrapolation of data derived at low pressure range to the condition of the outer core (>130 GPa) has to be applied, and may produce results that are far from the true numbers. However, at the point while the techniques are limited, studying the physical properties of the liquid-phase FeS at relatively low pressures still provides us a better picture of the physical behavior of the outer core comparing with data derived from solid state FeS experiments. Pervious studies on the viscosity of the Fe-FeS system (LeBlanc and Secco, 1996; Dobson et al., 2000; Urakawa et al., 2001; Secco et al., 2002) have presented different values of viscosity numbers with a maximum difference of two orders of magnitude. We have conducted the density measurements of liquid FeS (~36 wt% of S) up to 5.6 GPa in pressure and 1673K in temperature using the in-situ synchrotron-source x-ray absorption setup at Beamline X17B2, NSLS. The viscosity measurements were conducted by the x-ray radiograph technique combined with the falling sphere method. The falling sphere method applied at the experiment is suitable for liquids with viscosities between 10-3 Pa-s and 105 Pa-s (LeBlanc et al., 1999). We used tungsten spheres in our viscosity measurement experiments. We analyzed the sphere falling motion in the sample chamber at high pressure and high temperature. And by applying our density compression curve of liquid FeS to the Stokes?| viscometry method, we were able to derive the viscosity of liquid FeS.
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A thermodynamic recipe for baking the Earth's lower mantle and core as a whole
NASA Astrophysics Data System (ADS)
Tirone, Max; Faak, Kathi
2016-04-01
A rigorous understanding of the thermal and dynamic evolution of the core and the interaction with the silicate mantle cannot preclude a non-empirical petrological description of the problem which takes the form of a thermodynamic model. Because the Earth's core is predominantly made of iron such model may seem relatively straightforward, simply delivering a representation of the phase transformations in the P,T space. However due to well known geophysical considerations, a certain amount of light elements should be added. With the Occam's razor principle in mind, potential candidates could be the most abundant and easily accessible elements in the mantle, O, Si and Mg. Given these premises, the challenging problems on developing this type of model are: - a thermodynamic formulation should not simply describe phase equilibrium relations at least in the Fe-Si-O system (a formidable task itself) but should be also consistently applicable to evaluate thermophysical properties of liquid components and solids phases at extreme conditions (P=500-2000 kbar, T=1000-5000 K). Presently these properties are unknown for certain mineral and liquid components or partially available from scattered sources. - experimental data on the phase relations for iron rich liquid are extremely difficult to obtain and could not cover the entire P,T,X spectrum. - interaction of the outer core with the silicate mantle requires a melt model that is capable of describing a vast range of compositions ranging from metal-rich liquids to silicate liquids. The compound energy formalism for liquids with variable tendency to ionization developed by Hillert and coworkers is a sublattice model with varying stoichiometry that includes vacancies and neutral species in one site. It represents the ideal candidate for the task in hand. The thermodynamic model unfortunately is rather complex and a detailed description of the formulation for practical applications like chemical equilibrium calculations is nowhere to be found, while the model is only accessible on few commercial thermodynamic programs. The latest developments regarding all these related issues will be discussed in this contribution. In particular some self-consistent but preliminary results will be presented addressing the following topics: - some details regarding the implementation of the liquid model for Gibbs free energy minimizations, - the physically consistent behavior of thermodynamic properties of certain solid phases like (Fe,O,Si) BCC, FCC, HCP and liquid components, - selected phase diagrams at core conditions in the system Fe-Si-O, - derived geotherms linking the inner-outer core with the core-mantle boundary. - brief outline of the future geodynamic applications.
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Phosphorylation of p53 modifies sensitivity to ionizing radiation.
Okaichi, Kumio; Nose, Kanako; Kotake, Takako; Izumi, Nanaka; Kudo, Takashi
2011-06-01
Phosphorylation is an important modification involved in the control of p53 activity. We examined the relationship between p53 phosphorylation and cell radiosensitivity. We prepared H1299 cells (p53-null) with various mutations of p53 at three sites (serine 15, 20 and 46) and examined the radiosensitivity of the cells. In three mutant forms of p53--S15A, S20A and S46A--serine was converted to alanine at these sites to prevent phosphorylation, and in two other mutant forms, S15D and S20D, serine was converted to aspartic acid to mimic phosphorylation. H1299 cells were more radioresistant than cells with wild-type p53. Cells with the S15A and S46A mutant forms of p53 were radiosensitive, whereas those with the S15D, S20A and S20D forms showed medium radiosensitivity. Thus the sensitivity of cells to ionizing radiation varies according to the site of phosphorylation of p53.
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Miles, Edward F.; Tatsukawa, Yoshimi; Funamoto, Sachiyo; ...
2011-01-01
Purpose . There is evidence in the literature of increased maternal radiosensitivity during pregnancy. Materials and Methods . We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions . Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximatelymore » 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased radiosensitivity in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased radiosensitivity.« less
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Berg, Nora G; Pearce, Brady L; Rohrbaugh, Nathaniel; Jiang, Lin; Nolan, Michael W; Ivanisevic, Albena
2017-02-01
We report a composite biomaterial containing nanostructured GaOOH and Matrigel™ that can be modulated with respect to its stiffness and radiosensitization properties. A variety of concentrations of GaOOH were added to the composite to alter the mechanical properties of the material as well as to tune the radiosensitizing properties to the composite. PC-12 cells were used to study the combined effects of different stimuli on cell behavior. NGF was given to the cells to record their morphology as well as viability. An increase in the substrate stiffness caused an increase in neurite outgrowth but a decrease in cell viability. In addition, increasing the radiation dose decreased neurite outgrowth but increased cell viability when radiosensitizing particles were present. A subtractive effect between radiosensitizing and mechanical stimuli was observed when PC-12 cells were grown on the GaOOH containing composite. Copyright © 2016 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Wegierek-Ciuk, Aneta; Lankoff, Anna; Lisowska, Halina; Banasik-Nowak, Anna; Arabski, Michał; Kedzierawski, Piotr; Florek, Agnieszka; Wojcik, Andrzej
2010-01-01
It is well known that cancer patients receiving similar radiotherapy treatments differ widely in normal tissue reactions ranging from undetectable to unacceptably severe levels. Therefore, an important goal of radiobiological research is to establish a test which would allow identifying individual radiosensitivity of patients prior to radiotherapy. The aim of the presented study is to assess the relationship between lymphocyte intrinsic radiosensitivity in vitro and early reaction of normal tissue in cervix cancer patients treated by radiotherapy. The following endpoints are analyzed in vitro: frequency of micronuclei, the kinetics of DNA repair and apoptosis. Acute normal tissue reaction to radiotherapy in the skin, bladder and rectum are scored according to the EORTC/RTOG scale. Our results show a wide inter-individual variability in chromosomal radiosensitivity in vitro. The majority of patients show a Grade 0, 1 or 2 reaction for all organs studied. No statistically significant correlation has been observed between the in vitro results in lymphocytes and the degree of early normal tissue and organ reaction.
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Repurposing cephalosporin antibiotics as pro-senescent radiosensitizers
Flor, Amy C.; Sutton, Harold G.; Kron, Stephen J.; Weichselbaum, Ralph R.
2016-01-01
Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with radiosensitizers. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust radiosensitization in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic radiosensitizers to enhance the therapeutic ratio of radiotherapy. PMID:27129153
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Flanagan, Sheryl A., E-mail: sflan@umich.edu; Cooper, Kristin S.; Mannava, Sudha
Purpose: To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and radiosensitization and the mechanism by which these events occur. Methods and Materials: shRNA suppression of TS was compared with 5-fluoro-2 Prime -deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and radiosensitization were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquidmore » chromatography and as pSP189 plasmid mutations, respectively. Results: TS shRNA produced profound ({>=}90%) and prolonged ({>=}8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting radiosensitization (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. Conclusions: TS shRNA produced less cytotoxicity than FdUrd but was equally effective at radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit radiosensitization with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA mismatches underlying radiosensitization. Importantly, shRNA suppression of TS avoids FP-mediated TS elevation and its negative prognostic role. These studies support the further exploration of TS suppression as a novel radiosensitizing strategy.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Diagaradjane, P; Deorukhkar, A; Sankaranarayanapillai, M
2015-06-15
Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and inmore » vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x-rays using the active targeting strategy holds promise for clinical translation of this strategy from a toxicity and cost-effectiveness perspective and could evolve as a paradigm-changing approach in the field of radiation oncology.« less
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Thermal elastic properties of liquid Fe-C at high pressure
NASA Astrophysics Data System (ADS)
Shimoyama, Y.; Terasaki, H. G.; Urakawa, S.; Takubo, Y.; Watanuki, T.; Katayama, Y.; Kondo, T.
2015-12-01
Planetary outer core contains some light elements and these elements affect thermo-elastic parameters of pure iron. The effect of light elements on density and bulk modulus of liquid iron is necessary for estimating of these core compositions. Sound velocity of liquid iron alloys is also important for identifying light elements in the core by comparison with observed seismic data. We have measured sound velocity and density of liquid Fe-C simultaneously at high pressure. High pressure experiments were performed using a DIA-type cubic anvil press (SMAP-180) at BL22XU beamline, SPring-8 synchrotron in Japan. Sound velocity (VP) was measured using pulse-echo overlapping method (Higo et al., 2009). Density (ρ) was measured using X-ray absorption method (Katayama et al., 1993). We measured velocity and density of liquid Fe-C between 1.1-5.8 GPa and 1480-1700 K. Obtained density and velocity of Fe-C was found to increase with pressure. This study shows the VP of liquid Fe-C decreased with increasing temperature. Previous study of liquid Fe-S shows little change with increasing temperature at all pressure conditions (Nishida et al., 2013, Jing et al., 2014). We fit the relationship between VP and pressure using Murnaghan's equation of state. We obtained KS0 = 102.5(1.2) GPa, K'S = 5.2(0.4) at 1700 K. Comparison of the present data with previous study, KS is similar to liquid Fe but liquid Fe-S is small. We compared the relation between density and sound velocity of liquid Fe-C. We have found that the behavior of liquid Fe-C is similar to that of liquid Fe in the Birch's plot. The effect of carbon on liquid Fe is small on Birch's plot.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Qiang, Weiguang; Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou; Wu, Qinqin
Highlights: • Down-regulation of TPP1 shortened telomere length in telomerase-negative cells. • Down-regulation of TPP1 induced cell apoptosis in telomerase-negative cells. • Down-regulation of TPP1 increased radiosensitivity in telomerase-negative cells. - Abstract: Mammalian telomeres are protected by the shelterin complex that contains the six core proteins POT1, TPP1, TIN2, TRF1, TRF2 and RAP1. TPP1, formerly known as TINT1, PTOP, and PIP1, is a key factor that regulates telomerase recruitment and activity. In addition to this, TPP1 is required to mediate the shelterin assembly and stabilize telomere. Previous work has found that TPP1 expression was elevated in radioresistant cells and thatmore » overexpression of TPP1 led to radioresistance and telomere lengthening in telomerase-positive cells. However, the exact effects and mechanism of TPP1 on radiosensitivity are yet to be precisely defined in the ALT cells. Here we report on the phenotypes of the conditional deletion of TPP1 from the human osteosarcoma U2OS cells using ALT pathway to extend the telomeres.TPP1 deletion resulted in telomere shortening, increased apoptosis and radiation sensitivity enhancement. Together, our findings show that TPP1 plays a vital role in telomere maintenance and protection and establish an intimate relationship between TPP1, telomere and cellular response to ionizing radiation, but likely has the specific mechanism yet to be defined.« less
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Effect of anemia on tumor radiosensitivity under normo and hyperbaric conditions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rojas, A.; Stewart, F.A.; Smith, K.A.
1987-11-01
The effect of chronic anemia on tumor radiosensitivity in a murine tumor has been investigated. Anemia was induced by bilateral kidney irradiation given several months before tumor implantation. Anemic, anemic transfused, and normal non-anemic age-matched tumor bearing animals were irradiated with X rays (2 F/24 hr) either in air, air plus misonidazole, or under hyperbaric oxygen. The most resistant response was that of tumors grown in normal mice treated in air. Anemia produced an increase in radiosensitivity which was further enhanced by red blood cell replacement. The most sensitive overall response was seen in the anemic-transfused group treated with HBO.
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Effect of salt solutions on radiosensitivity of mammalian cells. I. Specific ion effects.
Raaphorst, G P; Kruuv, J
1977-07-01
The radiation isodose survival curve of cells subjected to a wide concentration range of sucrose solutions has two maxima separated by a minimum. Both cations and anions can alter the cellular radiosensitivity above and beyond the osmotic effect observed for cells treated with sucrose solutions. The basic shape of the isodose curve can also be modulated by changes in temperature and solution exposure times. Some of these alterations in radiosensitivity may be related to changes in the amount and structure of cellular water or macromolecular conformation or to the direct effect of the ions, expecially at high solute concentrations.
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Burnout and distribution of liquid between the flow core and wall films in narrow slot channels
NASA Astrophysics Data System (ADS)
Boltenko, E. A.; Shpakovskii, A. A.
2010-03-01
Previous works on studying distribution of liquid between the flow core and wall films in narrow slot channels are briefly reviewed. Interrelation between mass transfer processes and burnout is shown. A procedure for calculating burnout on convex and concave heat-transfer surfaces in narrow slot channels is presented.
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NASA Astrophysics Data System (ADS)
Shin, Jaesun; Kim, Beomjong; Jung, Wansu; Fahad, Mateen; Park, SangJin; Hong, Sung-Kyu
2017-05-01
Blue phase (BP) temperature range of a chiral nematic liquid crystal (LC) mixture is dependent upon the host nematic LC chemical structure and chiral dopant concentration. In this study, we investigated BP phase transition behaviour and helical twisting power (HTP) using three chiral dopant concentrations of cyano compound chiral nematic LC mixtures incorporating three two-ring core structures in the host nematic LCs. The effect of the host nematic LC core structure, HTP and chiral dopant concentrations were considered on BP temperature ranges, for two types of complete BPI and BPII without isotropic phase (Iso) and two types of coexistence state of BPI+Iso and BPII+Iso.
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Wigner, E.P.
1957-09-17
A reactor of the type having coolant liquid circulated through clad fuel elements geometrically arranged in a solid moderator, such as graphite, is described. The core is enclosed in a pressure vessel and suitable shielding, wherein means is provided for circulating vapor through the core to superheat the same. This is accomplished by drawing off the liquid which has been heated in the core due to the fission of the fuel, passing it to a nozzle within a chamber where it flashes into a vapor, and then passing the vapor through separate tubes extending through the moderator to pick up more heat developed in the core due to the fission of the fuel, thereby producing superheated vapor.
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Video Intertank for the Core Stage for the first SLS Flight
2017-06-29
This video shows the Space Launch System interank, which recently completed assembly at NASA's Michoud Assembly Facility in New Orleans. This tank was bolted together with more than 7,000 bolts. It is the only part of the SLS core stage assembly with bolts rather than by welding. The rocket's interank is located between the core stage liquid oxygen and liquid hydrogen fuel tanks. It has to be strong because the two SLS solid rocket boosters attache to the sides of it. This flight article will be connected to four other parts to form the core stage for the first integrated flight of SLS and Orion.
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Tunable optofluidic microring laser based on a tapered hollow core microstructured optical fiber.
Li, Zhi-Li; Zhou, Wen-Yuan; Luo, Ming-Ming; Liu, Yan-Ge; Tian, Jian-Guo
2015-04-20
A tunable optofluidic microring dye laser within a tapered hollow core microstructured optical fiber was demonstrated. The fiber core was filled with a microfluidic gain medium plug and axially pumped by a nanosecond pulse laser at 532 nm. Strong radial emission and low-threshold lasing (16 nJ/pulse) were achieved. Lasing was achieved around the surface of the microfluidic plug. Laser emission was tuned by changing the liquid surface location along the tapered fiber. The possibility of developing a tunable laser within the tapered simplified hollow core microstructured optical fiber presents opportunities for developing liquid surface position sensors and biomedical analysis.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Khateeb, Siddique; Su, Dong; Guerreo, Sandra
This article presents the performance of palladium-platinum core-shell catalysts (Pt/Pd/C) for oxygen reduction synthesized in gram-scale batches in both liquid cells and polymer-electrolyte membrane fuel cells. Core-shell catalyst synthesis and characterization, ink fabrication, and cell assembly details are discussed. The Pt mass activity of the Pt/Pd core-shell catalyst was 0.95 A mg –1 at 0.9 V measured in liquid cells (0.1 M HClO4), which was 4.8 times higher than a commercial Pt/C catalyst. The performances of Pt/Pd/C and Pt/C in large single cells (315 cm 2) were assessed under various operating conditions. The core-shell catalyst showed consistently higher performance thanmore » commercial Pt/C in fuel cell testing. A 20–60 mV improvement across the whole current density range was observed on air. Sensitivities to temperature, humidity, and gas composition were also investigated and the core-shell catalyst showed a consistent benefit over Pt under all conditions. However, the 4.8 times activity enhancement predicated by liquid cell measurements was not fully realized in fuel cells.« less
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Khateeb, Siddique; Su, Dong; Guerreo, Sandra; ...
2016-05-03
This article presents the performance of palladium-platinum core-shell catalysts (Pt/Pd/C) for oxygen reduction synthesized in gram-scale batches in both liquid cells and polymer-electrolyte membrane fuel cells. Core-shell catalyst synthesis and characterization, ink fabrication, and cell assembly details are discussed. The Pt mass activity of the Pt/Pd core-shell catalyst was 0.95 A mg –1 at 0.9 V measured in liquid cells (0.1 M HClO4), which was 4.8 times higher than a commercial Pt/C catalyst. The performances of Pt/Pd/C and Pt/C in large single cells (315 cm 2) were assessed under various operating conditions. The core-shell catalyst showed consistently higher performance thanmore » commercial Pt/C in fuel cell testing. A 20–60 mV improvement across the whole current density range was observed on air. Sensitivities to temperature, humidity, and gas composition were also investigated and the core-shell catalyst showed a consistent benefit over Pt under all conditions. However, the 4.8 times activity enhancement predicated by liquid cell measurements was not fully realized in fuel cells.« less
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Controlled release liquid dosage formulation
Benton, Ben F.; Gardner, David L.
1989-01-01
A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Meng, Zhen; Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081; Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn
2015-05-01
Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocationmore » and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.« less
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NASA Astrophysics Data System (ADS)
Falk, Martin; Horakova, Zuzana; Svobodova, Marketa; Masarik, Michal; Kopecna, Olga; Gumulec, Jaromir; Raudenska, Martina; Depes, Daniel; Bacikova, Alena; Falkova, Iva; Binkova, Hana
2017-09-01
In order to improve patients' post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor radiosensitivity is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the radiosensitivity of tumors. We compared formation and decrease of γH2AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with 2 Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures - CD90-, CD90+, and a mixed culture of these cells - were isolated from 1 clinically radioresistant, 2 radiosensitive, and 4 undetermined HPV-HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the radiosensitive tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance.
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Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo
2017-08-15
Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.
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Wada, Seiichi; Van Khoa, Tran; Kobayashi, Yasuhiko; Funayama, Tomoo; Ogihara, Kikumi; Ueno, Shunji; Ito, Nobuhiko
2005-11-01
Diseases of companion animals are shifting from infectious diseases to neoplasms (cancer), and since radiation therapy is one of the effective choices available for cancer treatment, the application of radiotherapy in veterinary medicine is likely to increase. However tumor tissues have different radiosensitivities, and therefore it is important to determine the intrinsic radiosensitivity of tumors in individual patients in advance of radiotherapy. We have studied the relationship between the surviving cell fraction measured by a clonogenic assay and DNA double strand breaks detected by a comet assay under neutral conditions in three canine tumor cell lines, after gamma-ray and carbon ion irradiation. In all the cell lines, cell death assessed by the clonogenic assay was much higher following irradiation with carbon ions than with gamma-rays. The initial and residual (4 hr) DNA damage due to gamma-ray and carbon ion irradiation were higher in a radiosensitive cell line than in a radioresistant cell line. The surviving cell fraction at 2 Gy (SF2) showed a tendency for correlation with both the initial and residual DNA damage. In particular, the residual damage per Gy was significantly correlated with SF2, regardless of the type of radiation. This indicates that cellular radiosensitivity can be predicted by detection of radiation-induced residual DNA damage.
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Roadmap to clinical use of gold nanoparticles for radiosensitization
Schuemann, J.; Berbeco, R.; Chithrani, B. D.; Cho, S.; Kumar, R.; McMahon, S.; Sridhar, S.; Krishnan, S.
2015-01-01
The past decade has seen a dramatic increase in interest in the use of Gold Nanoparticles (GNPs) as radiation sensitizers for radiotherapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs’ efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X-rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiosensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes and preparations. As a result, mechanisms of uptake and radiosensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiosensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage. PMID:26700713
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Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-κB signaling pathway.
Li, Gang; Wang, Ziming; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen
2017-10-01
The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by western blot analysis. The results showed that curcumin significantly increased radiosensitivity of ACHN cells by inhibiting the cell proliferation and DNA damage repair, causing cell cycle arrest at G2/M phase, inducing apoptosis in vitro, and suppressing the growth of xenografts in vivo. In addition, curcumin enhanced radiosensitivity was through markedly inhibiting IR-induced NF-κB signaling by modulating the related protein expressions including NF-κBP65, I-κB, VEGF, COX2, and Bcl-2 in ACHN cells, which was further strengthened by NF-κB inhibitor PDTC treatment. Thus, curcumin may confer radiosensitivity on RCC via inhibition of NF-κB activation and its downstream regulars, suggesting the potential application of curcumin as an adjuvant in radiotherapy of RCC. Copyright © 2017. Published by Elsevier Masson SAS.
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Warenius, H. M.; Jones, M.; Jones, M. D.; Browning, P. G.; Seabra, L. A.; Thompson, C. C.
1998-01-01
We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 proto-oncogene, intrinsic cellular radiosensitivity and rapid exit from a G2/M delay induced by 2 Gy of gamma-irradiation. Raf1 is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G1/S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Raf1 protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G2/M populations after 2 Gy of gamma-irradiation. Differences in intrinsic radiosensitivity after modulation of the G1/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Raf1 expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009). PMID:9579826
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Debeb, Bisrat G.; Xu Wei; Mok, Henry
2010-03-01
Purpose: It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres. Methods and Materials: We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cellmore » transcription factors. Results: 3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA radiosensitized adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres. Conclusion: We have concluded that VA might preferentially radiosensitize differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and radiosensitizers.« less
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Saito, Y; Mishima, K; Tobita, Y; Suzuki, T; Matsubayashi, M
2004-10-01
To establish reasonable safety concepts for the realization of commercial liquid-metal fast breeder reactors, it is indispensable to demonstrate that the release of excessive energy due to re-criticality of molten core could be prevented even if a severe core damage accident took place. Two-phase flow due to the boiling of fuel-steel mixture in the molten core pool has a larger liquid-to-gas density ratio and higher surface tension in comparison with those of ordinary two-phase flows such as air-water flow. In this study, to investigate the effect of the recirculation flow on the bubble behavior, visualization and measurement of nitrogen gas-molten lead bismuth in a rectangular tank was performed by using neutron radiography and particle image velocimetry techniques. Measured flow parameters include flow regime, two-dimensional void distribution, and liquid velocity field in the tank. The present technique is applicable to the measurement of velocity fields and void fraction, and the basic characteristics of gas-liquid metal two-phase mixture were clarified.
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Thermal Equation of State of Iron: Constraint on the Density Deficit of Earth's Core
NASA Astrophysics Data System (ADS)
Fei, Y.; Murphy, C. A.; Shibazaki, Y.; Huang, H.
2013-12-01
The seismically inferred densities of Earth's solid inner core and the liquid outer core are smaller than the measured densities of solid hcp-iron and liquid iron, respectively. The inner core density deficit is significantly smaller than the outer core density deficit, implying different amounts and/or identities of light-elements incorporated in the inner and outer cores. Accurate measurements of the thermal equation-of-state of iron over a wide pressure and temperature range are required to precisely quantify the core density deficits, which are essential for developing a quantitative composition model for the core. The challenge has been evaluating the experimental uncertainties related to the choice of pressure scales and the sample environment, such as hydrostaticity at multi-megabar pressures and extreme temperatures. We have conducted high-pressure experiments on iron in MgO, NaCl, and Ne pressure media and obtained in-situ X-ray diffraction data up to 200 GPa at room temperature. Using inter-calibrated pressure scales including the MgO, NaCl, Ne, and Pt scales, we have produced a consistent compression curve of hcp-Fe at room temperature. We have also performed laser-heated diamond-anvil cell experiments on both Fe and Pt in a Ne pressure medium. The experiment was designed to quantitatively compare the thermal expansion of Fe and Pt in the same sample environment using Ne as the pressure medium. The thermal expansion data of hcp-Fe at high pressure were derived based on the thermal equation of state of Pt. Using the 300-K isothermal compression curve of iron derived from our static experiments as a constraint, we have developed a thermal equation of state of hcp-Fe that is consistent with the static P-V-T data of iron and also reproduces the shock wave Hugoniot data for pure iron. The thermodynamic model, based on both static and dynamic data, is further used to calculate the density and bulk sound velocity of liquid iron. Our results define the solid inner core and liquid outer core density deficits, which can serve as the basis for any core composition models.
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NASA Astrophysics Data System (ADS)
Jing, Z.; Wang, Y.; Kono, Y.; Yu, T.; Sakamaki, T.; Park, C.; Rivers, M. L.; Sutton, S. R.; Shen, G.
2013-12-01
Geophysical observations based on lunar seismology and laser ranging strongly suggest that the Moon's iron core is partially molten. Similar to Earth and other terrestrial planets, light elements, such as sulfur, silicon, carbon, and oxygen, are likely present in the lunar core. Determining the light element concentration in the outer core is of vital importance to the understanding of the structure, dynamics, and chemical evolution of the Moon, as well as the enigmatic history of the lunar dynamo. Among the candidate elements, sulfur is the preferred major light element in the lunar outer due to its high abundance in the parent bodies of iron meteorites, its high solubility in liquid Fe at the lunar core pressure (~5 GPa), and its strong effects on reducing the density, velocity, and freezing temperature of the core. In this study, we conducted in-situ sound velocity measurements on liquid samples of four different compositions, including pure Fe, Fe-10wt%S, Fe-20wt%S, and Fe-27wt%S, at pressure and temperature conditions up to 8 GPa and 1973 K (encompassing the entire lunar depth range), using the Kawai-type multi-anvil device at the GSECARS beamline 13-ID-D and the Paris-Edinburgh cell at HPCAT beamline 16-BM-B. Our results show that the velocity of Fe-rich liquids increases upon compression, decreases with increasing sulfur content, and is nearly independent of temperature. Compared to the seismic velocity of the outer core, our velocity data constrain the sulfur content at 4×2 wt%, indicating a significantly denser (6.4×0.4 g/cm3) and hotter (1860×60 K) outer core than previously estimated. A new lunar structure model incorporating available geophysical observations points to a smaller core radius. Our model also suggests a top-down solidification scenario for the evolution of the lunar core. Such an 'iron snow' process may have been an important mechanism for the growth of the inner core.
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The effect of oxygen on density of liquid iron at high pressure
NASA Astrophysics Data System (ADS)
Takubo, Y.; Terasaki, H.; Shimoyama, Y.; Urakawa, S.; Suzuki, A.; Nishida, K.; Kamuro, R.; Kishimoto, S.; Kondo, T.; Ohtani, E.; Yoshinori, K.
2012-12-01
The Earth's outer core has been thought to be composed of liquid iron alloys with 10 % of light elements, such as sulfur, carbon, silicon and oxygen. Density of liquid iron alloy is one of the key parameters to understand the composition and structure of the Earth's outer core. The effect of various light elements (e.g., S, Si, and C) on the density of liquid iron at high pressure and high temperature has been studied (Nishida et al., 2011; Tateyama et al., 2011 Sanloup et al., 2011; Terasaki et al., 2010). It was revealed that the density depression is quite different depending on dissolving light element. However the effect of oxygen on the density of liquid iron has not been investigated due to high liquidus temperature of Fe-O system, although oxygen is one of the major candidates of the light elements in the Earth's outer core (e.g., Ringwood, 1977). Oxygen could be incorporated into the core during early terrestrial evolution (Corgne et al., 2009). In this study, we have measured the density of liquid Fe-O in the pressure and temperature ranges of 2.3-3.0 GPa and 2000-2250 K using X-ray absorption method. High pressure experiment was performed using a cubic-type multi-anvil press installed at BL22XU of the SPring-8 synchrotron radiation facility in Japan. Monochromatic X-ray of 35 keV was used. Mixture of Fe and FeO powders with 0.5 wt% oxygen, which corresponds to the eutectic composition at 3 GPa (Ohtani et al., 1984) was used as a sample. The sample was inserted in a single crystal sapphire capsule. The obtained density of this study is 6.7 g/cm3 at 3 GPa and 2005 K. Compared to the density of pure liquid iron (Anderson and Ahrens, 1994) at the present experimental condition, the density of liquid Fe-O is about 5.3 % smaller than that of pure liquid iron. On the other hand, thermal expansion coefficient of liquid Fe-O shows similar value to that of liquid iron.
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Electrokinetic detection for X-ray spectra of weakly interacting liquids: n-decane and n-nonane.
Lam, Royce K; Shih, Orion; Smith, Jacob W; Sheardy, Alex T; Rizzuto, Anthony M; Prendergast, David; Saykally, Richard J
2014-06-21
The introduction of liquid microjets into soft X-ray absorption spectroscopy enabled the windowless study of liquids by this powerful atom-selective high vacuum methodology. However, weakly interacting liquids produce large vapor backgrounds that strongly perturb the liquid signal. Consequently, solvents (e.g., hydrocarbons, ethers, ketones, etc.) and solutions of central importance in chemistry and biology have been inaccessible by this technology. Here we describe a new detection method, upstream detection, which greatly reduces the vapor phase contribution to the X-ray absorption signal while retaining important advantages of liquid microjet sample introduction (e.g., minimal radiation damage). The effectiveness of the upstream detection method is demonstrated in this first study of room temperature liquid hydrocarbons: n-nonane and n-decane. Good agreement with first principles' calculations indicates that the eXcited electron and Core Hole theory adequately describes the subtle interactions in these liquids that perturb the electronic structure of the unoccupied states probed in core-level experiments.
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Wide range optofluidically tunable multimode interference fiber laser
NASA Astrophysics Data System (ADS)
Antonio-Lopez, J. E.; Sanchez-Mondragon, J. J.; LiKamWa, P.; May-Arrioja, D. A.
2014-08-01
An optofluidically tunable fiber laser based on multimode interference (MMI) effects with a wide tuning range is proposed and demonstrated. The tunable mechanism is based on an MMI fiber filter fabricated using a special fiber known as no-core fiber, which is a multimode fiber (MMF) without cladding. Therefore, when the MMI filter is covered by liquid the optical properties of the no-core fiber are modified, which allow us to tune the peak wavelength response of the MMI filter. Rather than applying the liquid on the entire no-core fiber, we change the liquid level along the no-core fiber, which provides a highly linear tuning response. In addition, by selecting the adequate refractive index of the liquid we can also choose the tuning range. We demonstrate the versatility of the optofluidically tunable MMI filter by wavelength tuning two different gain media, erbium doped fiber and a semiconductor optical amplifier, achieving tuning ranges of 55 and 90 nm respectively. In both cases, we achieve side-mode suppression ratios (SMSR) better than 50 dBm with output power variations of less than 0.76 dBm over the whole tuning range.
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Pretest analysis document for Semiscale Test S-LH-1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shaw, R.A.
Results from various pretest calculations which were performed for Test S-LH-1 are included in this report. Test S-LH-1 has been designed to produce primary liquid holdup in the steam generator U-tubes similar to Tests S-UT-8. The analyses included in this report indicate liquid will be held in the tubes, the core liquid level will be appropriately depressed, and a core heater rod temperature excursion should occur. Several sensitivity studies are also included which identify parameters which could affect the response.
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Melting Experiments in the Fe-FeSi System at High Pressure
NASA Astrophysics Data System (ADS)
Ozawa, H.; Hirose, K.
2013-12-01
The principal light element in the Earth's core must reproduce the density jump at the inner core boundary (ICB). Silicon is thought to be a plausible light element in the core, and the melting phase relations in Fe-FeSi binary system at the ICB pressure are of great importance. Theoretical calculations on the Fe-FeSi binary system suggested that the difference in Si content between the outer core and the inner core would be too small to satisfy the observed density jump at the ICB [Alfè et al., 2002 EPSL], which requires other light elements in addition to silicon. Here we experimentally examined partitioning of silicon between liquid and solid iron up to 97 GPa. High pressure and temperature conditions were generated in a laser-heated diamond-anvil cell. Chemical compositions of co-existing quenched liquid and solid Fe-Si alloys were determined with a field-emission-type electron probe micro-analyzer. We used Fe-Si alloy containing 9 wt% Si as a starting material. Chemical analyses on the recovered samples from 39 and 49 GPa demonstrated the coexistence of quenched Si-depleted liquid and Si-enriched solid. In contrast, silicon partitions preferentially into liquid metal at 97 GPa, suggesting the starting composition (Fe-9wt% Si) lies on the iron-rich part of the eutectic. These results indicate the eutectic composition shifts toward FeSi between 49 and 97 GPa.
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Liquid Film Migration in Warm Formed Aluminum Brazing Sheet
NASA Astrophysics Data System (ADS)
Benoit, M. J.; Whitney, M. A.; Wells, M. A.; Jin, H.; Winkler, S.
2017-10-01
Warm forming has previously proven to be a promising manufacturing route to improve formability of Al brazing sheets used in automotive heat exchanger production; however, the impact of warm forming on subsequent brazing has not previously been studied. In particular, the interaction between liquid clad and solid core alloys during brazing through the process of liquid film migration (LFM) requires further understanding. Al brazing sheet comprised of an AA3003 core and AA4045 clad alloy, supplied in O and H24 tempers, was stretched between 0 and 12 pct strain, at room temperature and 523K (250 °C), to simulate warm forming. Brazeability was predicted through thermal and microstructure analysis. The rate of solid-liquid interactions was quantified using thermal analysis, while microstructure analysis was used to investigate the opposing processes of LFM and core alloy recrystallization during brazing. In general, liquid clad was consumed relatively rapidly and LFM occurred in forming conditions where the core alloy did not recrystallize during brazing. The results showed that warm forming could potentially impair brazeability of O temper sheet by extending the regime over which LFM occurs during brazing. No change in microstructure or thermal data was found for H24 sheet when the forming temperature was increased, and thus warm forming was not predicted to adversely affect the brazing performance of H24 sheet.
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Day, Clifford K.; Stringer, James L.
1977-01-01
Apparatus for measuring displacements of core components of a liquid metal fast breeder reactor by means of an eddy current probe. The active portion of the probe is located within a dry thimble which is supported on a stationary portion of the reactor core support structure. Split rings of metal, having a resistivity significantly different than sodium, are fixedly mounted on the core component to be monitored. The split rings are slidably positioned around, concentric with the probe and symmetrically situated along the axis of the probe so that motion of the ring along the axis of the probe produces a proportional change in the probes electrical output.
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Wheeler, J.A.
1957-11-01
A design of a reactor is presented in which the fuel elements may be immersed in a liquid coolant when desired without the necessity of removing them from the reactor structure. The fuel elements, containing the fissionable material are in plate form and are disposed within spaced slots in a moderator material, such as graphite to form the core. Adjacent the core is a tank containing the liquid coolant. The fuel elements are mounted in spaced relationship on a rotatable shaft which is located between the core and the tank so that by rotation of the shaft the fuel elements may be either inserted in the slots in the core to sustain a chain reaction or immersed in the coolant.
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Earth's core-mantle boundary - Results of experiments at high pressures and temperatures
NASA Technical Reports Server (NTRS)
Knittle, Elise; Jeanloz, Raymond
1991-01-01
Laboratory experiments document that liquid iron reacts chemically with silicates at high pressures (above 2.4 x 10 to the 10th Pa) and temperatures. In particular, (Mg,Fe)SiO3 perovskite, the most abundant mineral of earth's lower mantle, is expected to react with liquid iron to produce metallic alloys (FeO and FeSi) and nonmetallic silicates (SiO2 stishovite and MgSiO3 perovskite) at the pressures of the core-mantle boundary, 14 x 10 to the 10th Pa. The experimental observations, in conjunction with seismological data, suggest that the lowermost 200 to 300 km of earth's mantle, the D-double-prime layer, may be an extremely heterogeneous region as a result of chemical reactions between the silicate mantle and the liquid iron alloy of earth's core. The combined thermal-chemical-electrical boundary layer resulting from such reactions offers a plausible explanation for the complex behavior of seismic waves near the core-mantle boundary and could influence earth's magnetic field observed at the surface.
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NASA Technical Reports Server (NTRS)
Righter, K.; Pando, K.; Danielson, L. R.; Humayun, M.
2017-01-01
Earth's core contains approximately 10% of a light element that is likely a combination of S, C, Si, and O, with Si possibly being the most abundant light element. Si dissolved into Fe liquids can have a large effect on the magnitude of the activity coefficient of siderophile elements (SE) in Fe liquids, and thus the partitioning behavior of those elements between core and mantle. The effect of Si can be small such as for Ni and Co, or large such as for Mo, Ge, Sb, As. The effect of Si on many siderophile elements is unknown yet could be an important, and as yet unquantified, influence on the core-mantle partitioning of SE. Here we report new experiments designed to quantify the effect of Si on the partitioning of Pt (with Re and Ru in progress or planned) between metal and silicate melt. The results will be applied to Earth, for which we have excellent constraints on the mantle Pt concentrations.
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NASA Technical Reports Server (NTRS)
Righter, K.; Pando, K.; Danielson, L. R.; Humayun, M.; Righter, M.; Lapen, T.; Boujibar, A.
2016-01-01
Earth's core contains approximately 10 percent light elements that are likely a combination of S, C, Si, and O, with Si possibly being the most abundant. Si dissolved into Fe liquids can have a large effect on the magnitude of the activity coefficient of siderophile elements (SE) in Fe liquids, and thus the partitioning behavior of those elements between core and mantle. The effect of Si can be small such as for Ni and Co, or large such as for Mo, Ge, Sb, As. The effect of Si on many siderophile elements is unknown yet could be an important, and as yet unquantified, influence on the core-mantle partitioning of SE. Here we report new experiments designed to quantify the effect of Si on the partitioning of P, Au, Pd, and many other SE between metal and silicate melt. The results will be applied to Earth, for which we have excellent constraints on the mantle siderophile element concentrations.
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USDA-ARS?s Scientific Manuscript database
The Minimum Inhibitory Concentration (MIC) of basil oil, was determined for two pathogenic fungi of rice, Aspergillus niger and Penicillium chrysogenum. The antifungal activity of the basil oil in combination with ionising radiation was then investigated to determine if basil oil caused radiosensit...
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Everything Old Is New Again: Using Nelfinavir to Radiosensitize Rectal Cancer
Meyn, Raymond E.; Krishnan, Sunil; Skinner, Heath D.
2016-01-01
Summary Repurposing agents approved for other indications to radiosensitize tumors may be advantageous. The study by Hill and colleagues utilizes Nelfinavir, an HIV protease inhibitor, in combination with radiotherapy in rectal cancer in a prospective study. This combination may improve tumor perfusion and regression compared to radiotherapy alone. PMID:26920893
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Liquid uranium alloy-helium fission reactor
Minkov, V.
1984-06-13
This invention describes a nuclear fission reactor which has a core vessel and at least one tandem heat exchanger vessel coupled therewith across upper and lower passages to define a closed flow loop. Nuclear fuel such as a uranium alloy in its liquid phase fills these vessels and flow passages. Solid control elements in the reactor core vessel are adapted to be adjusted relative to one another to control fission reaction of the liquid fuel therein. Moderator elements in the other vessel and flow passages preclude fission reaction therein. An inert gas such as helium is bubbled upwardly through the heat exchanger vessel operable to move the liquid fuel upwardly therein and unidirectionally around the closed loop and downwardly through the core vessel. This helium gas is further directed to heat conversion means outside of the reactor vessels to utilize the heat from the fission reaction to generate useful output. The nuclear fuel operates in the 1200 to 1800/sup 0/C range, and even higher to 2500/sup 0/C.
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NASA Astrophysics Data System (ADS)
Wajs, Jan; Mikielewicz, Dariusz
2017-03-01
Detailed studies have suggested that the critical heat flux in the form of dryout in minichannels occurs when the combined effects of entrainment, deposition, and evaporation of the film make the film flow rate go gradually and smoothly to zero. Most approaches so far used the mass balance equation for the liquid film with appropriate formulations for the rate of deposition and entrainment respectively. It must be acknowledged that any discrepancy in determination of deposition and entrainment rates, together with cross-correlations between them, leads to the loss of accuracy of model predictions. Conservation equations relating the primary parameters are established for the liquid film and vapor core. The model consists of three mass balance equations, for liquid in the film as well as two-phase core and the gas phase itself. These equations are supplemented by the corresponding momentum equations for liquid in the film and the two-phase core. Applicability of the model has been tested on some experimental data.
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Synthetic nanoparticles for delivery of radioisotopes and radiosensitizers in cancer therapy.
Zhao, Jun; Zhou, Min; Li, Chun
2016-01-01
Radiotherapy has been, and will continue to be, a critical modality to treat cancer. Since the discovery of radiation-induced cytotoxicity in the late 19th century, both external and internal radiation sources have provided tremendous benefits to extend the life of cancer patients. Despite the dramatic improvement of radiation techniques, however, one challenge persists to limit the anti-tumor efficacy of radiotherapy, which is to maximize the deposited dose in tumor while sparing the rest of the healthy vital organs. Nanomedicine has stepped into the spotlight of cancer diagnosis and therapy during the past decades. Nanoparticles can potentiate radiotherapy by specifically delivering radionuclides or radiosensitizers into tumors, therefore enhancing the efficacy while alleviating the toxicity of radiotherapy. This paper reviews recent advances in synthetic nanoparticles for radiotherapy and radiosensitization, with a focus on the enhancement of in vivo anti-tumor activities. We also provide a brief discussion on radiation-associated toxicities as this is an area that, up to date, has been largely missing in the literature and should be closely examined in future studies involving nanoparticle-mediated radiosensitization.
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Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells
Kesler, Cristina T.; Kuo, Angera; Wong, Hon-Kit; Masuck, David J.; Shah, Jennifer L.; Kozak, Kevin; Held, Kathryn D.; Padera, Timothy P.
2013-01-01
Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the radiosensitivity of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC radiosensitivity was also examined. Vascular endothelial growth factor (VEGF)-C enhanced radiosensitivity when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and G2/M phases. These LECs showed higher levels of H2A.X—an indicator of DNA damage—after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence. PMID:24201897
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Nahas, Shareef A.; Davies, Robert; Fike, Francesca; Nakamura, Kotoka; Du, Liutao; Kayali, Refik; Martin, Nathan T.; Concannon, Patrick; Gatti, Richard A.
2015-01-01
In an effort to explore the possible causes of human radiosensitivity and identify more rapid assays for cellular radiosensitivity, we interrogated a set of assays that evaluate cellular functions involved in recognition and repair of DNA double-strand breaks: (1) neutral comet assay, (2) radiation-induced γ-H2AX focus formation, (3) the temporal kinetics of structural maintenance of chromosomes 1 phosphorylation, (4) intra-S-phase checkpoint integrity, and (5) mitochondrial respiration. We characterized a unique panel of 19 “radiosensitive” human lymphoblastoid cell lines from individuals with undiagnosed diseases suggestive of a DNA repair disorder. Radiosensitivity was defined by reduced cellular survival using a clonogenic survival assay. Each assay identified cell lines with defects in DNA damage response functions. The highest concordance rate observed, 89% (17/19), was between an abnormal neutral comet assay and reduced survival by the colony survival assay. Our data also suggested that the neutral comet assay would be a more rapid surrogate for analyzing DNA repair/processing disorders. PMID:21962002
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A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer.
Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther
2016-06-14
Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.
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Process to make core-shell structured nanoparticles
Luhrs, Claudia; Phillips, Jonathan; Richard, Monique N
2014-01-07
Disclosed is a process for making a composite material that contains core-shell structured nanoparticles. The process includes providing a precursor in the form of a powder a liquid and/or a vapor of a liquid that contains a core material and a shell material, and suspending the precursor in an aerosol gas to produce an aerosol containing the precursor. In addition, the process includes providing a plasma that has a hot zone and passing the aerosol through the hot zone of the plasma. As the aerosol passes through the hot zone of the plasma, at least part of the core material and at least part of the shell material in the aerosol is vaporized. Vapor that contains the core material and the shell material that has been vaporized is removed from the hot zone of the plasma and allowed to condense into core-shell structured nanoparticles.
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NASA Astrophysics Data System (ADS)
An, Seongpil; Liou, Minho; Song, Kyo Yong; Jo, Hong Seok; Lee, Min Wook; Al-Deyab, Salem S.; Yarin, Alexander L.; Yoon, Sam S.
2015-10-01
Coaxial electrospinning was used to fabricate two types of core-shell fibers: the first type with liquid resin monomer in the core and polyacrylonitrile in the shell, and the second type with liquid curing agent in the core and polyacrylonitrile in the shell. These two types of core-shell fibers were mutually entangled and embedded into two flexible transparent matrices thus forming transparent flexible self-healing composite materials. Such materials could be formed before only using emulsion electrospinning, rather than coaxial electrospinning. The self-healing properties of such materials are associated with release of healing agents (resin monomer and cure) from nanofiber cores in damaged locations with the subsequent polymerization reaction filing the micro-crack with polydimethylsiloxane. Transparency of these materials is measured and the anti-corrosive protection provided by them is demonstrated in electrochemical experiments.
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NASA Astrophysics Data System (ADS)
de Jong, B. H.
2007-12-01
Variations in surface tension affect the buoyancy of objects floating in a liquid. Thus an object floating in water will sink deeper in the presence of dishwater fluid. This is a very minor but measurable effect. It causes for instance ducks to drown in aqueous solutions with added surfactant. The surface tension of liquid iron is very strongly affected by the presence of sulfur which acts as a surfactant in this system varying between 1.9 and 0.4 N/m at 10 mass percent Sulfur (Lee & Morita (2002), This last value is inferred to be the maximum value for Sulfur inferred to be present in the liquid outer core. Venting of Sulfur from the liquid core manifests itself on the Earth surface by the 105 to 106 ton of sulfur vented into the atmosphere annually (Wedepohl, 1984). Inspection of surface Sulfur emission indicates that venting is non-homogeneously distributed over the Earth's surface. The implication of such large variation in surface tension in the liquid outer core are that at locally low Sulfur concentration, the liquid outer core does not wet the predominantly MgSiO3 matrix with which it is in contact. However at a local high in Sulfur, the liquid outer core wets this matrix which in the fluid state has a surface tension of 0.4 N/m (Bansal & Doremus, 1986), couples with it, and causes it to sink. This differential and diapiric movement is transmitted through the essentially brittle mantle (1024 Pa.s, Lambeck & Johnson, 1998; the maximum value for ice being about 1030 Pa.s at 0 K, in all likely hood representing an upper bound of viscosity for all materials) and manifests itself on the surface by the roughly 20 km differentiation, about 0.1 % of the total mantle thickness, between topographical heights and lows with concomitant lateral movement in the crust and upper mantle resulting in thin skin tectonics. The brittle nature of the medium though which this movement is transmitted suggests that the extremes in topography of the D" layer are similar in range to those observed on the Earth's surface and are mimicked by lows under the oceans and highs under the altiplanos. Careful and area selective S wave core mantle ellipsometry might be able to discern these core-mantle topographic variations. As such this process demonstrates the validity of the Gaia hypothesis enunciated by Baas Becking(1931) that no ecological niche on our planet is closed off from other niches "nothing in the world is single".
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NASA Astrophysics Data System (ADS)
Deproost, Marie-Hélène; Rivoldini, Attilio; Van Hoolst, Tim
2016-10-01
Remote sensing data of Mercury's surface by MESSENGER indicate that Mercury formed under reducing conditions. As a consequence, silicon is likely the main light element in the core together with a possible small fraction of sulfur. Compared to sulfur, which does almost not partition into solid iron at Mercury's core conditions and strongly decreases the melting temperature, silicon partitions almost equally well between solid and liquid iron and is not very effective at reducing the melting temperature of iron. Silicon as the major light element constituent instead of sulfur therefore implies a significantly higher core liquidus temperature and a decrease in the vigor of compositional convection generated by the release of light elements upon inner core formation.Due to the immiscibility in liquid Fe-Si-S at low pressure (below 15 GPa), the core might also not be homogeneous and consist of an inner S-poor Fe-Si core below a thinner Si-poor Fe-S layer. Here, we study the consequences of a silicon-rich core and the effect of the blanketing Fe-S layer on the thermal evolution of Mercury's core and on the generation of a magnetic field.
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Huang, Ai; Yao, Jing; Liu, Tao; Lin, Zhenyu; Zhang, Sheng; Zhang, Tao; Ma, Hong
2018-04-01
This study aimed to investigate the influence of the expression of P53-binding protein 1 (53BP1), a key component in DNA damage repair pathways, on the radiosensitizing effect of icotinib hydrochloride in colorectal cancer and to elucidate the mechanisms underlying this influence. Real-time RT-PCR and Western blotting were performed to verify the gene-knockout effect of 53BP1 small hairpin RNA (ShRNA), and colony formation assay was employed to investigate the influence of 53BP1 downregulation on the radiosensitizing effect of icotinib hydrochloride in HCT116 cells. Cell apoptosis, cell cycle distributions, and histone H2AX (γ-H2AX) fluorescence foci after 53BP1 knockdown were evaluated. Relative protein expression in the ataxia telangiectasia mutated kinase (ATM)-checkpoint kinase-2 (CHK2)-P53 pathway was measured by Western blot analysis to unravel the molecular mechanisms linking the pathway to the above phenomena. Icotinib hydrochloride increased the radiosensitivity of HCT116 cells; however, this effect was suppressed by the downregulation of 53BP1 expression, a change that inhibited cell apoptosis, increased the percentage of HCT116 cells arrested in S-phase and inhibited the protein expression of key molecules in the ATM-CHK2-P53 apoptotic pathway. Our studies confirmed that the loss of 53BP1 serves as a negative regulator of the radiosensitizing effect of icotinib in part by suppressing the ATM-CHK2-P53 apoptotic pathway.
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Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi
2014-01-01
Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation. PMID:24899803
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Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi
2014-01-01
Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation.
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WE-G-BRE-08: Radiosensitization by Olaparib Eluting Nanospheres
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tangutoori, S; Kumar, R; Sridhar, S
2014-06-15
Purpose: Permanent prostate brachytherapy often uses inert bio-absorbable spacers to achieve the desired geometric distribution of sources within the prostate. Transforming these spacers into implantable nanoplatforms for chemo-radiation therapy (INCeRT) provides a means of providing sustained in-situ release of radiosensitizers in the prostate to enhance the therapeutic ratio of the procedure. Olaparib, a PARP inhibitor, suppresses DNA repair processes present during low dose rate continuous irradiation. This work investigates the radiosensitizing/DNA damage repair inhibition by NanoOlaparib eluting nanospheres. Methods: Human cell line PC3 (from ATCC), was maintained in F12-k medium supplemented with fetal bovine serum. Clonogenic assay kit (from Fischermore » Scientific) was used to fix and stain the cells to determine the long term effects of irradiation. Nanoparticle size and zeta potential of nanospheres were determined using a Zeta particle size analyzer. The incorporation of Olaparib in nanospheres was evaluated by HPLC. Irradiation was performed in a small animal irradiator operating at 220 KeV.The long term effects of radio-sensitization with olaparib and nanoolaparib was determined using the clonogenic assay at 2 Gy and 4 Gy doses. The cells were allowed to grow for around 10 doubling cycles, The colonies were fixed and stained using clonogenic assay kit. The excess stain was washed off using DI water and the images were taken using a digital camera. Results: Radiosensitization studies were carried out in prostate cancer cell line, PC3 radiation at 0, 2 and 4Gy doses. Strongest dose response was observed with nanoolaparib treated cells compared to untreated cells. Conclusion: A two stage drug release of drug eluting nanospheres from a biodegradable spacer has been suggested for sustained in-situ release of Olaparib to suppress DNA repair processes during prostate brachytherapy. The Olaparib eluting nanospheres had the same in-vitro radiosensitizing effect as free olaparib. DOD 1R21CA16977501, A. David Mazzone Awards Program 2012PD164.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bigdeli, Bahareh, E-mail: bhr.bigdeli@ut.ac.ir
Introduction: Radiotherapy is a potent treatment against breast cancer, which is the most commonly diagnosed cancer among women. However, the emergence of radioresistance due to increased DNA repair leads to radiotherapeutic failure. Applying polyphenols combined with radiation is a more promising method leading to better survival. Enterolactone, a phytoestrogenic polyphenol, has been reported to inhibit an important radioresistance signaling pathway, therefore we conjectured that enterolactone could enhance radiosensitivity in breast cancer. To assess this hypothesis, radiation response of enterolactone treated MDA-MB-231 and T47D cell lines and corresponding cellular mechanisms were investigated. Methods: Cytotoxicity of enterolactone was measured via MTT assay.more » Cells were treated with enterolactone before X-irradiation, and clonogenic assay was used to evaluate radiosensitivity. Cell cycle distribution and apoptosis were measured by flow cytometric analysis. In addition, DNA damages and corresponding repair, chromosomal damages, and aberrations were assessed by comet, micronucleus, and cytogenetic assays, respectively. Results: Enterolactone decreased the viability of cells in a concentration- and time dependent manner. Enterolactone significantly enhanced radiosensitivity of cells by abrogating G2/M arrest, impairing DNA repair, and increasing radiation-induced apoptosis. Furthermore, increased chromosomal damages and aberrations were detected in cells treated with enterolactone combined with X-rays than X-ray alone. These effects were more prominent in T47D than MDA-MB-231 cells. Discussion: To our knowledge, this is the first report that enterolactone is a novel radiosensitizer for breast cancer irrespective of estrogen receptor status. Authors propose enterolactone as a candidate for combined therapy to decrease the radiation dose delivered to patients and subsequent side effects. - Highlights: • Enterolactone is proposed to be a novel radiosensitizer for human breast cancer. • Enterolactone pretreatment enhances radiation induced apoptosis. • Enterolactone pretreatment impairs repair of radiation-induced DNA damages. • Chromosomal aberrations increases in cells receiving enterolactone and X-ray. • Micronuclei formation is elevated after combined treatment with enterolactone.« less
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Rotational modes of a simple Earth model
NASA Astrophysics Data System (ADS)
Seyed-Mahmoud, B.; Rochester, M. G.; Rogister, Y. J. G.
2017-12-01
We study the tilt-over mode (TOM), the spin-over mode (SOM), the free core nutation (FCN), and their relationships to each other using a simple Earth model with a homogeneous and incompressible liquid core and a rigid mantle. Analytical solutions for the periods of these modes as well as that of the Chandler wobble is found for the Earth model. We show that the FCN is the same mode as the SOM of a wobbling Earth. The reduced pressure, in terms of which the vector momentum equation is known to reduce to a scalar second order differential equation (the so called Poincaŕe equation), is used as the independent variable. Analytical solutions are then found for the displacement eigenfucntions in a meridional plane of the liquid core for the aforementioned modes. We show that the magnitude of motion in the mantle during the FCN is comparable to that in the liquid core, hence very small. The displacement eigenfunctions for these aforementioned modes as well as those for the free inner core nutation (FICN), computed numerically, are also given for a three layer Earth model which also includes a rigid but capable of wobbling inner core. We will discuss the slow convergence of the period of the FICN in terms of the characteristic surfaces of the Poincare equation.
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NASA Astrophysics Data System (ADS)
Benoit, Michael J.; Whitney, Mark A.; Wells, Mary A.; Winkler, Sooky
2016-09-01
Isothermal solidification (IS) is a phenomenon observed in clad aluminum brazing sheets, wherein the amount of liquid clad metal is reduced by penetration of the liquid clad into the core. The objective of the current investigation is to quantify the rate of IS through the use of a previously derived parameter, the Interface Rate Constant (IRC). The effect of peak temperature and initial sheet temper on IS kinetics were investigated. The results demonstrated that IS is due to the diffusion of silicon (Si) from the liquid clad layer into the solid core. Reduced amounts of liquid clad at long liquid duration times, a roughened sheet surface, and differences in resolidified clad layer morphology between sheet tempers were observed. Increased IS kinetics were predicted at higher temperatures by an IRC model as well as by experimentally determined IRC values; however, the magnitudes of these values are not in good agreement due to deficiencies in the model when applied to alloys. IS kinetics were found to be higher for sheets in the fully annealed condition when compared with work-hardened sheets, due to the influence of core grain boundaries providing high diffusivity pathways for Si diffusion, resulting in more rapid liquid clad penetration.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Haudebourg, Raphael; Fichet, Pascal; Goutelard, Florence
The detection (location and quantification) of nuclear facilities to be dismantled possible contamination with low-range particles emitters ({sup 3}H, other low-energy β emitters, a emitters) remains a tedious and expensive task. Indeed, usual remote counters show a too low sensitivity to these non-penetrating radiations, while conventional wipe tests are irrelevant for fixed radioactivity evaluation. The only method to accurately measure activity levels consists in sampling and running advanced laboratory analyses (spectroscopy, liquid scintillation counting, pyrolysis...). Such measurements generally induce sample preparation, waste production (destructive analyses, solvents), nuclear material transportation, long durations, and significant labor mobilization. Therefore, the search for themore » limitation of their number and cost easily conflicts with the necessity to perform a dense screening for sampling (to maximize the representativeness of the samples), in installations of thousands of square meters (floors, wells, ceilings), plus furniture, pipes, and other wastes. To overcome this contradiction, Digital Autoradiography (D. A.) was re-routed from bio molecular research to radiological mapping of nuclear installations under dismantling and to waste and sample analysis. After in-situ exposure to the possibly-contaminated areas to investigate, commercial reusable radiosensitive phosphor screens (of a few 100 cm{sup 2}) were scanned in the proper laboratory device and sharp quantitative images of the radioactivity could be obtained. The implementation of geostatistical tools in the data processing software enabled the exhaustive characterization of concrete floors at a rate of 2 weeks / 100 m{sup 2}, at lowest costs. Various samples such as drilled cores, or tank and wood pieces, were also successfully evaluated with this method, for decisive results. Thanks to the accurate location of potential contamination spots, this approach ensures relevant and representative sampling for further laboratory analyses and should be inserted in the range of common tools used in dismantling. (authors)« less
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Gravitational Core-Mantle Coupling and the Acceleration of the Earth
NASA Technical Reports Server (NTRS)
Rubincam, David Parry; Smith, David E. (Technical Monitor)
2001-01-01
Gravitational core-mantle coupling may be the cause of the observed variable acceleration of the Earth's rotation on the 1000 year timescale. The idea is that density inhomogeneities which randomly come and go in the liquid outer core gravitationally attract density inhomogeneities in the mantle and crust, torquing the mantle and changing its rotation state. The corresponding torque by the mantle on the core may also explain the westward drift of the magnetic field of 0.2 deg per year. Gravitational core-mantle coupling would stochastically affect the rate of change of the Earth's obliquity by just a few per cent. Its contribution to polar wander would only be about 0.5% the presently observed rate. Tidal friction is slowing down the rotation of the Earth, overwhelming a smaller positive acceleration from postglacial rebound. Coupling between the liquid outer core of the Earth and the mantle has long been a suspected reason for changes in the length-of-day. The present investigation focuses on the gravitational coupling between the density anomalies in the convecting liquid outer core and those in the mantle and crust as a possible cause for the observed nonsecular acceleration on the millenial timescale. The basic idea is as follows. There are density inhomogeneities caused by blobs circulating in the outer core like the blobs in a lava lamp; thus the outer core's gravitational field is not featureless. Moreover, these blobs will form and dissipate somewhat randomly. Thus there will be a time variability to the fields. These density inhomogeneities will gravitationally attract the density anomalies in the mantle.
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Jang, Bum-Sup; Kim, In Ah
2017-09-01
We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset. To validate the gene signature, 1045 patients were selected and divided into two clusters using a consensus clustering algorithm based on their radiosensitive (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1. Patents assigned to the RS group had decreased risk of recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (HR 0.45, 95% CI 0.25-0.81, p=0.008) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p<0.001) than the RR group. In the PD-L1-high group, the RS group was associated with better RFS compared to the RR group (HR 0.37, 95% CI 0.16-0.87, p=0.022) in multivariate analysis. The level of PD-L1 expression may represent the immunogenicity of tumors, and thus, we speculated that the PD-L1-high group had more immunogenic tumors, which could be more sensitive to radiation-induced immunologic cell death. We first evaluated the predictive value of the radiosensitivity gene signature and described a relationship with this radiosensitivity gene signature and PD-L1. The radiosensitivity gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1 therapy. Copyright © 2017 Elsevier B.V. All rights reserved.
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Yi, Hanjie; Yan, Xianglei; Luo, Qiuyun; Yuan, Luping; Li, Baoxia; Pan, Wentao; Zhang, Lin; Chen, Haibo; Wang, Jing; Zhang, Yubin; Zhai, Yifan; Qiu, Miao-Zhen; Yang, Da-Jun
2018-05-02
Gastric cancer is the leading cause of cancer related death worldwide. Radiation alone or combined with chemotherapy plays important role in locally advanced and metastatic gastric adenocarcinoma. MDM2-p53 interaction and downstream signaling affect cellular response to DNA damage which leads to cell cycle arrest and apoptosis. Therefore, restoring p53 function by inhibiting its interaction with MDM2 is a promising therapeutic strategy for cancer. APG-115 is a novel small molecule inhibitor which blocks the interaction of MDM2 and p53. In this study, we investigated that the radiosensitivity of APG-115 in gastric adenocarcinoma in vitro and in vivo. The role of APG-115 in six gastric cancer cells viability in vitro was determined by CCK-8 assay. The expression level of MDM2, p21, PUMA and BAX in AGS and MKN45 cell lines was measured via real-time PCR (RT-PCR). The function of treatment groups on cell cycle and cell apoptosis were detected through Flow Cytometry assay. Clonogenic assays were used to measure the radiosensitivity of APG-115 in p53 wild type gastric cancer cell lines. Western blot was conducted to detect the protein expressions of mdm2-p53 signal pathway. Xenograft models in nude mice were established to explore the radiosensitivity role of APG-115 in gastric cancer cells in vivo. We found that radiosensitization by APG-115 occurred in p53 wild-type gastric cancer cells. Increasing apoptosis and cell cycle arrest was observed after administration of APG-115 and radiation. Radiosensitivity of APG-115 was mainly dependent on MDM2-p53 signal pathway. In vivo, APG-115 combined with radiation decreased xenograft tumor growth much more significantly than either single treatment. Moreover, the number of proliferating cells (Ki-67) significantly decreased in combination group compared with single treatment group. In summary, we found that combination of MDM2-p53 inhibitor (APG-115) and radiotherapy can enhance antitumor effect both in vitro and in vivo. This is the first report on radiosensitivity of APG-115 which shed light on clinical trial of the combination therapy of radiation with APG-115 in gastric adenocarcinoma.
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The radiation response of human dermal fibroblasts
NASA Astrophysics Data System (ADS)
Mitchell, Stephen Andrew
A clinically reliable predictive assay based on normal-tissue radiosensitivity may lead to improved tumour control through individualised dose prescriptions. In-vitro fibroblast radiosensitivity has been shown, in several studies, to correlate with late radiation morbidity. The aim of this study was to investigate some of the cellular mechanisms underlying the normal-tissue response. In this study, seventeen primary fibroblast strains were established by enzymatic disaggregation of skin biopsies obtained from patients. These comprised seven who experienced acute tissue reactions to radiotherapy, four patients with a normal response and six non-cancer volunteers. An AT cell line was included as a positive control for radiosensitivity. In-vitro radiosensitivity was measured using a clonogenic assay at both high (HDR: 1.6 Gymin-1) and low dose rate (LDR: 0.01 Gymin-1). The radiation parameter HDR SF2 was the most sensitive in discriminating the seven sensitive patients from the remaining ten normal patients (range 0.11-0.19 sensitive patients compared with 0.17-0.34 control patients: p<0.0001). Neither the use of an internal control or LDR radiation protocol increased this discrimination. Pulsed-field gel electrophoresis (PFGE) was used to measure the level of initial and residual double-strand breaks following irradiation. No correlation was found between HDR SF2 and initial DNA damage. However, a strong correlation was found between clonogenic survival and both residual DNA damage (measured over 10-70 Gy, allowing 4 h repair, correlation coefficient: 0.90, <0.0001) and the ratio of residual/initial DNA damage, with the sensitive cell lines generally showing a higher level of residual DNA damage. Cell-cycle delays were found in all 18 cell strains in response to 2 Gy irradiation, but were not found to discriminate between sensitive and normal patients. Associated studies found no mutations of the ATM gene in the five radiosensitive patients studied. However, a coding sequence alteration was found in the XRCC1 gene in one of the radiosensitive patients. These findings indicate that a DNA repair defect may be partly responsible for the extreme reactions to radiotherapy observed in a small percentage of patients and that with further modifications, an assay based on measurement of residual DNA damage may form the basis of a predictive test for radiosensitivity.
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Future Seismic Constraints on Mercury's Core Composition
NASA Astrophysics Data System (ADS)
Knibbe, J. S.; Luginbhuel, S. M.; Rivoldini, A.; Kono, Y.; Van Hoolst, T.; van Westrenen, W.
2018-05-01
The composition of Mercury's large core is strongly linked to the planet's origin and magnetic field generation. We present P-wave velocity measurements for liquid Fe-Si and Fe-S metals. A future seismic mission can constrain the core composition.
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The effects of nickel and sulphur on the core-mantle partitioning of oxygen in Earth and Mars
NASA Astrophysics Data System (ADS)
Tsuno, Kyusei; Frost, Daniel J.; Rubie, David C.
2011-03-01
Constraints on the partitioning of oxygen between silicates, oxides, and metallic liquids are important for determining the amount of oxygen that may have entered the cores of terrestrial planets and to identify likely reactions at the core-mantle boundary. Several previous studies have examined oxygen partitioning between liquid Fe metal and ferropericlase, however, the cores of terrestrial planets also contain nickel and most likely sulphur. We have performed experiments to examine the effects of both nickel and sulphur on the partitioning of oxygen between ferropericlase and liquid Fe alloy up to pressures of 24.5 GPa in the temperature range 2430-2750 K using a multianvil press. The results show that at a fixed oxygen fugacity the proportion of oxygen that partitions into liquid metal will decrease by approximately 1-2 mol% on the addition of 10-20 mol% nickel to the liquid. The addition of around 30 mol% sulphur will, on the other hand, increase the metal oxygen content by approximately 10 mol%. Experiments to examine the combined effects of both nickel and sulphur, show a decrease in the effect of nickel on oxygen partitioning as the sulphur content of the metal increases. We expand an existing thermodynamic model for the partitioning of oxygen at high pressures and temperatures to include the effects of nickel and sulphur by fitting these experimental data, with further constraints provided by existing phase equilibria studies at similar conditions in the Fe-S and Fe-O-S systems. Plausible terrestrial core sulphur contents have little effect on oxygen partitioning. When our model is extrapolated to conditions of the present day terrestrial core-mantle boundary, the presence of nickel is found to lower the oxygen content of the outer core that is in equilibrium with the expected mantle ferropericlase FeO content, by approximately 1 weight %, in comparison to nickel free calculations. In agreement with nickel-free experiments, this implies that the Earth's outer core is undersaturated in oxygen with respect to plausible mantle FeO contents, which will result in either the depletion of FeO from the base of the mantle or cause the development of an outer core layer that is enriched in oxygen. The oxygen content of the more sulphur-rich Martian core would be in the range 2-4 wt.% if it is in equilibrium with the FeO-rich Martian mantle.
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NASA Astrophysics Data System (ADS)
Ohishi, Yuji; Kondo, Toshiki; Ishikawa, Takehiko; Okada, Junpei T.; Watanabe, Yuki; Muta, Hiroaki; Kurosaki, Ken; Yamanaka, Shinsuke
2017-03-01
It is important to understand the behaviors of molten core materials to investigate the progression of a core meltdown accident. In the early stages of bundle degradation, low-melting-temperature liquid phases are expected to form via the eutectic reaction between Zircaloy and stainless steel. The main component of Zircaloy is Zr and those of stainless steel are Fe, Ni, and Cr. Our group has previously reported physical property data such as viscosity, density, and surface tension for Zr-Fe liquid alloys using an electrostatic levitation technique. In this study, we report the viscosity, density, and surface tension of Zr-Ni and Zr-Cr liquid alloys (Zr1-xNix (x = 0.12 and 0.24) and Zr0.77Cr0.23) using the electrostatic levitation technique.
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On the recovery of electric currents in the liquid core of the Earth
NASA Astrophysics Data System (ADS)
Kuslits, Lukács; Prácser, Ernő; Lemperger, István
2017-04-01
Inverse geodynamo modelling has become a standard method to get a more accurate image of the processes within the outer core. In this poster excerpts from the preliminary results of an other approach are presented. This comes around the possibility of recovering the currents within the liquid core directly, using Main Magnetic Field data. The approximation of different systems of the flow of charge is possible with various geometries. Based on previous geodynamo simulations, current coils can furnish a good initial geometry for such an estimation. The presentation introduces our preliminary test results and the study of reliability of the applied inversion algorithm for different numbers of coils, distributed in a grid simbolysing the domain between the inner-core and core-mantle boundaries. We shall also present inverted current structures using Main Field model data.
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NASA Technical Reports Server (NTRS)
Smilenov, L. B.; Brenner, D. J.; Hall, E. J.
2001-01-01
Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulation.
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Constraining Mercury's interior structure with geodesy data and its present thermal state
NASA Astrophysics Data System (ADS)
Rivoldini, Attilio; Van Hoolst, Tim; Noack, Lena
2015-04-01
Recent measurements of Mercury's spin state and gravitational field supplemented by the assumption that the planet's core is made of iron and sulfur give strong constraints on its interior structure. In particular, they allow a precise determination of Mercury's core size and average mantle density. Present geodesy data do, however, almost not constrain the size of the inner core. Interior structure models with a fully molten liquid core as well as models with an inner core almost as large as the core agree with the observations. Additionally, the observed internally generated magnetic field of Mercury does not preclude the absence of an inner core, since remelting of iron snow inside the core could produce a sufficient buoyancy flux to drive magnetic field generation by compositional convection. Although sulfur is ubiquitously invoked as being the principal candidate light element in terrestrial planet's cores its abundance in the core depends on the redox conditions during planetary formation. Remote sensing data of Mercury's surface by MESSENGER indicate that Mercury formed under reducing conditions. As a consequence, substantial amounts of other light elements like for example silicon and carbon could be present together with sulfur inside Mercury's core. Compared to sulfur, which does almost not partition into solid iron at Mercury's core conditions, silicon partitions almost equally well between solid and liquid iron whereas a few percent of carbon can partition into solid iron. Therefore, compared to a pure iron-sulfur core, if silicon and carbon are present in the core the density jump at the inner-core outer-core boundary could be smaller and induce a large enough change in the inner-core flattening to alter Mercury's libration amplitude. Moreover, the presence of carbon together with sulfur further reduces the core solidus temperature, potentially delaying the onset of inner core formation. Finally, if both silicon and sulfur are present in sufficient quantities a thin layer much enriched in sulfur and depleted in silicon could form at the top of the core as a consequence of a large immiscibility region in liquid Fe-S-Si at Mercury's core conditions. The present radius of an inner core depends mainly on Mercury's thermal state and concentration of light elements inside the core. Because of the secular cooling of the planet, at a time in Mercury's evolution the temperature inside the core drops below the core liquidus temperature somewhere in the core, which can lead to the formation of an inner core and to the global contraction of the planet. The amount of contraction depends mainly on the temperature decrease, on the thermal expansion of the materials inside the planet, on the volume of crystallized iron-rich core liquid, and on the volume of crystallized crust. In this study we use geodesy data (88 day libration amplitude, polar moment of inertia, and tidal Love number), the recent estimate about the radial contraction of Mercury, and thermo-chemical evolution calculations taking into account the formation of the crust, a growing inner core, and modeling the formation of iron-rich snow in the core in order to improve our knowledge about Mercury's inner core radius and thermal state. Since data from remote sensing of Mercury's surface indicate that Mercury formed under reducing conditions we consider models that have sulfur, silicon, and carbon as light elements inside their core.
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Robust microfluidic encapsulation of cholesteric liquid crystals toward photonic ink capsules.
Lee, Sang Seok; Kim, Bomi; Kim, Su Kyung; Won, Jong Chan; Kim, Yun Ho; Kim, Shin-Hyun
2015-01-27
Robust photonic microcapsules are created by microfluidic encapsulation of cholesteric liquid crystals with a hydrogel membrane. The membrane encloses the cholesteric core without leakage in water and the core exhibits pronounced structural colors. The photonic ink capsules, which have a precisely controlled bandgap position and size, provide new opportunities in colorimetric micro-thermometers and optoelectric applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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High sensitivity optical fiber liquid level sensor based on a compact MMF-HCF-FBG structure
NASA Astrophysics Data System (ADS)
Zhang, Yunshan; Zhang, Weigang; Chen, Lei; Zhang, Yanxin; Wang, Song; Yan, Tieyi
2018-05-01
An ultra-high sensitivity fiber liquid level sensor based on wavelength demodulation is proposed and demonstrated. The sensor is composed of a segment of multimode fiber and a large aperture hollow-core fiber assisted by a fiber Bragg grating (FBG). Interference occurs due to core mismatching and different modes with different effective refractive indices. The experimental results show that the liquid level sensitivity of the sensor is 1.145 nm mm‑1, and the linearity is up to 0.996. The dynamic temperature compensation of the sensor can be achieved by cascading an FBG. Considering the high sensitivity and compact structure of the sensor, it can be used for real-time intelligent monitoring of tiny changes in liquid level.
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Frydel, Derek; Levin, Yan
2018-01-14
In the present work, we investigate a gas-liquid transition in a two-component Gaussian core model, where particles of the same species repel and those of different species attract. Unlike a similar transition in a one-component system with particles having attractive interactions at long separations and repulsive interactions at short separations, a transition in the two-component system is not driven solely by interactions but by a specific feature of the interactions, the correlations. This leads to extremely low critical temperature, as correlations are dominant in the strong-coupling limit. By carrying out various approximations based on standard liquid-state methods, we show that a gas-liquid transition of the two-component system poses a challenging theoretical problem.
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NASA Astrophysics Data System (ADS)
Frydel, Derek; Levin, Yan
2018-01-01
In the present work, we investigate a gas-liquid transition in a two-component Gaussian core model, where particles of the same species repel and those of different species attract. Unlike a similar transition in a one-component system with particles having attractive interactions at long separations and repulsive interactions at short separations, a transition in the two-component system is not driven solely by interactions but by a specific feature of the interactions, the correlations. This leads to extremely low critical temperature, as correlations are dominant in the strong-coupling limit. By carrying out various approximations based on standard liquid-state methods, we show that a gas-liquid transition of the two-component system poses a challenging theoretical problem.
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Bayart, Emilie; Pouzoulet, Frédéric; Calmels, Lucie; Dadoun, Jonathan; Allot, Fabien; Plagnard, Johann; Ravanat, Jean-Luc; Bridier, André; Denozière, Marc; Bourhis, Jean; Deutsch, Eric
2017-01-01
Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a halogenated pyrimidine analog combined with low-energy X-ray therapy.
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NASA Astrophysics Data System (ADS)
Williams, Q. C.; Manghnani, M. H.
2017-12-01
The convective style of planetary cores is critically dependent on the thermal properties of iron alloys. In particular, the relation between the adiabatic gradient and the melting curve governs whether planetary cores solidify from their top down (when the adiabat is steeper than the melting curve) or the bottom up (the converse). Molten iron alloys, in general, have large, ambient pressure thermal expansions: values in excess of 1.2 x 10^-4/K are dictated by data derived from levitated and sessile drop techniques. These high values of the thermal expansion imply that the adiabatic gradients within early planetesimals and present day moons that have comparatively low-pressure, iron-rich cores are steep (typically greater than 35 K/GPa at low pressures): values, at low pressures, that are greater than the slope of the melting curve, and hence show that the cores of small solar system objects probably crystallize from the top-down. Here, we deploy a different manifestation of these large values of thermal expansion to determine the pressure dependence of thermal expansion in iron-rich liquids: a difficult parameter to experimentally measure, and critical for determining the size range of cores in which top-down core solidification predominates. In particular, the difference between the adiabatic and isothermal bulk moduli of iron liquids is in the 20-30% range at the melting temperature, and scales as the product of the thermal expansion, the Grüneisen parameter, and the temperature. Hence, ultrasonic (and adiabatic) moduli of iron alloy liquids, when coupled with isothermal sink-float measurements, can yield quantitative constraints on the pressure dependence of thermal expansion. For liquid iron alloys containing 17 wt% Si, we find that the thermal expansion is reduced by 50% over the first 8 GPa of compression. This "squeezing out" of the anomalously high low-pressure thermal expansion of iron-rich alloys at relatively modest conditions likely limits the size range over which top-down crystallizing cores are anticipated within planetary bodies.
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Compaction-Driven Evolution of Pluto's Rocky Core: Implications for Water-Rock Interactions
NASA Astrophysics Data System (ADS)
Gabasova, L. R.; Tobie, G.; Choblet, G.
2018-05-01
We model the compaction of Pluto's rocky core after accretion and explore the potential for hydrothermal circulation within the porous layer, as well as examine its effect on core cooling and the persistence of a liquid internal ocean.
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Simulation of the planetary interior differentiation processes in the laboratory.
Fei, Yingwei
2013-11-15
A planetary interior is under high-pressure and high-temperature conditions and it has a layered structure. There are two important processes that led to that layered structure, (1) percolation of liquid metal in a solid silicate matrix by planet differentiation, and (2) inner core crystallization by subsequent planet cooling. We conduct high-pressure and high-temperature experiments to simulate both processes in the laboratory. Formation of percolative planetary core depends on the efficiency of melt percolation, which is controlled by the dihedral (wetting) angle. The percolation simulation includes heating the sample at high pressure to a target temperature at which iron-sulfur alloy is molten while the silicate remains solid, and then determining the true dihedral angle to evaluate the style of liquid migration in a crystalline matrix by 3D visualization. The 3D volume rendering is achieved by slicing the recovered sample with a focused ion beam (FIB) and taking SEM image of each slice with a FIB/SEM crossbeam instrument. The second set of experiments is designed to understand the inner core crystallization and element distribution between the liquid outer core and solid inner core by determining the melting temperature and element partitioning at high pressure. The melting experiments are conducted in the multi-anvil apparatus up to 27 GPa and extended to higher pressure in the diamond-anvil cell with laser-heating. We have developed techniques to recover small heated samples by precision FIB milling and obtain high-resolution images of the laser-heated spot that show melting texture at high pressure. By analyzing the chemical compositions of the coexisting liquid and solid phases, we precisely determine the liquidus curve, providing necessary data to understand the inner core crystallization process.
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Simulation of the Planetary Interior Differentiation Processes in the Laboratory
Fei, Yingwei
2013-01-01
A planetary interior is under high-pressure and high-temperature conditions and it has a layered structure. There are two important processes that led to that layered structure, (1) percolation of liquid metal in a solid silicate matrix by planet differentiation, and (2) inner core crystallization by subsequent planet cooling. We conduct high-pressure and high-temperature experiments to simulate both processes in the laboratory. Formation of percolative planetary core depends on the efficiency of melt percolation, which is controlled by the dihedral (wetting) angle. The percolation simulation includes heating the sample at high pressure to a target temperature at which iron-sulfur alloy is molten while the silicate remains solid, and then determining the true dihedral angle to evaluate the style of liquid migration in a crystalline matrix by 3D visualization. The 3D volume rendering is achieved by slicing the recovered sample with a focused ion beam (FIB) and taking SEM image of each slice with a FIB/SEM crossbeam instrument. The second set of experiments is designed to understand the inner core crystallization and element distribution between the liquid outer core and solid inner core by determining the melting temperature and element partitioning at high pressure. The melting experiments are conducted in the multi-anvil apparatus up to 27 GPa and extended to higher pressure in the diamond-anvil cell with laser-heating. We have developed techniques to recover small heated samples by precision FIB milling and obtain high-resolution images of the laser-heated spot that show melting texture at high pressure. By analyzing the chemical compositions of the coexisting liquid and solid phases, we precisely determine the liquidus curve, providing necessary data to understand the inner core crystallization process. PMID:24326245
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Inhibition of Hsp27 Radiosensitizes Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guttmann, David M.; Hart, Lori; Du, Kevin
Purpose: To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Methods and Materials: Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH2AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Results: Hsp27 LNA and Hsp27 shRNA radiosensitized head-and-neck cancer cellmore » lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the radiosensitizing effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. Conclusions: These results support a radiosensitizing property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer.« less
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Medhat, Amina M; Azab, Khaled Sh; Said, Mahmoud M; El Fatih, Neama M; El Bakary, Nermeen M
2017-10-01
Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.
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Silibinin preferentially radiosensitizes prostate cancer by inhibiting DNA repair signaling
Nambiar, Dhanya K.; Rajamani, Paulraj; Deep, Gagan; Jain, Anil K.; Agarwal, Rajesh; Singh, Rana P.
2015-01-01
Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective radiosensitizer, we studied the radiosensitizing effects and associated mechanisms of silibinin in prostate cancer (PCa). The radiosensitizing effect of silibinin with ionizing radiation (IR) was assessed on radioresistant PCa cell lines by clonogenic, cell cycle, cell death and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μM) enhanced IR (2.5-10 Gy)-caused inhibition (up to 96%, P<0.001) of colony formation selectively in PCa cells, and prolonged and enhanced IR-caused G2/M arrest, apoptosis and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/2) and EGFR signaling and attenuated the levels of anti-apoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H2AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly radiosensitized DU145 tumor xenograft inhibition (84%, P<0.01) with higher apoptotic response (10-fold, P<0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced pro-survival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Since silibinin is already in phase II clinical trial for PCa patients, the present finding has translational relevance for radioresistant PCa. PMID:26516160
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Inhibition of Hsp27 radiosensitizes head-and-neck cancer by modulating deoxyribonucleic acid repair.
Guttmann, David M; Hart, Lori; Du, Kevin; Seletsky, Andrew; Koumenis, Constantinos
2013-09-01
To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH2AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Hsp27 LNA and Hsp27 shRNA radiosensitized head-and-neck cancer cell lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the radiosensitizing effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. These results support a radiosensitizing property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer. Copyright © 2013. Published by Elsevier Inc.
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Localized delivery of chemotherapy to the cervix for radiosensitization.
Hodge, Lucy S; Downs, Levi S; Chura, Justin C; Thomas, Sajeena G; Callery, Patrick S; Soisson, A Patrick; Kramer, Paul; Wolfe, Stephen S; Tracy, Timothy S
2012-10-01
Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of radiosensitizing agents. However, administration of radiosensitizing chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of radiosensitizing chemotherapeutics to the cervix while limiting systemic toxicities. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CerviPrep™). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite 2',2'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/g tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/g tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for radiosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.
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Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.
Someya, Masanori; Sakata, Koh-ichi; Matsumoto, Yoshihisa; Tauchi, Hiroshi; Kai, Masahiro; Hareyama, Masato; Fukushima, Masakazu
2012-01-01
Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.
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Andrographolide radiosensitizes human esophageal cancer cell line ECA109 to radiation in vitro.
Wang, Z-M; Kang, Y-H; Yang, X; Wang, J-F; Zhang, Q; Yang, B-X; Zhao, K-L; Xu, L-P; Yang, L-P; Ma, J-X; Huang, G-H; Cai, J; Sun, X-C
2016-01-01
To explore the radiosensitivity of andrographolide on esophageal cancer cell line ECA109. The inhibition effects of andrographolide were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Clonogenic survival assay was used to evaluate the effects of andrographolide on the radiosensitivity of esophageal cancer cells. Immunofluorescence was employed to examine Bax expression. The changes in cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of NF-κb/Cleaved-Caspase3/Bax/Bcl-2 was measured using Western blot analysis. DNA damage was detected via γ-H2AX foci counting. With a clear dose and time effects, andrographolide was found to inhibit the proliferation of esophageal cell line ECA109. The results of the clonogenic survival assay show that andrographolide could markedly enhance radiosensitivity (P < 0.05) with a sensitizing enhancement ratio of 1.28. Andrographolide caused a dose-dependent increase in Cleaved-Caspase3/Bax protein expression and a decrease in Bcl-2/NF-κb expression. Apoptosis in andrographolide-treated ECA-109 increased significantly compared with the apoptosis in the simple drug and radiation combined with drug groups (P < 0.001; P < 0.05). Moreover, compared with the independent radiation group, the andrographolide combined with radiation group increased the number of DNA double chain breaks. Andrographolide can increase the radiosensitivity of esophageal cell line ECA109. This result may be associated with the decrease in the NF-κb level and the induced apoptosis of esophageal cancer cells. © 2014 International Society for Diseases of the Esophagus.
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Khoshgard, Karim; Kiani, Parvaneh; Haghparast, Abbas; Hosseinzadeh, Leila; Eivazi, Mohammad Taghi
2017-08-01
The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.
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Rosiglitazone enhances the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chiu, Shu-Jun, E-mail: chiusj@mail.tcu.edu.tw; Institute of Radiation Sciences, Tzu Chi Technology College, Hualien, Taiwan; Hsaio, Ching-Hui
2010-04-09
Combined-modality treatment has improved the outcome in cases of various solid tumors, and radiosensitizers are used to enhance the radiotherapeutic efficiency. Rosiglitazone, a synthetic ligand of peroxisome proliferator-activated receptors {gamma} used in the treatment of type-2 diabetes, has been shown to reduce tumor growth and metastasis in human cancer cells, and may have the potential to be used as a radiosensitizer in radiotherapy for human colorectal cancer cells. In this study, rosiglitazone treatment significantly reduced the cell viability of p53-wild type HCT116 cells but not p53-mutant HT-29 cells. Interestingly, rosiglitazone pretreatment enhanced radiosensitivity in p53-mutant HT-29 cells but not HCT116more » cells, and prolonged radiation-induced G{sub 2}/M arrest and enhanced radiation-induced cell growth inhibition in HT-29 cells. Pretreatment with rosiglitazone also suppressed radiation-induced H2AX phosphorylation in response to DNA damage and AKT activation for cell survival; on the contrary, rosiglitazone pretreatment enhanced radiation-induced caspase-8, -9, and -3 activation and PARP cleavage in HT-29 cells. In addition, pretreatment with a pan-caspase inhibitor, zVAD-fmk, attenuated the levels of caspase-3 activation and PARP cleavage in radiation-exposed cancer cells in combination with rosiglitazone pretreatment. Our results provide proof for the first time that rosiglitazone suppresses radiation-induced survival signals and DNA damage response, and enhances the radiation-induced apoptosis signaling cascade. These findings can assist in the development of rosiglitazone as a novel radiosensitizer.« less
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Eady, J. J.; Peacock, J. H.; McMillan, T. J.
1992-01-01
DNA repair processes play an important role in the determination of radiation response in both normal and tumour cells. We have investigated one aspect of DNA repair in a number of human cell lines of varying radiosensitivity using the adenovirus 5 host cell reactivation assay (HCR). In this technique, gamma-irradiated virions are used to infect cells and the ability of the cellular repair systems to process this damage is assayed by a convenient immunoperoxidase method recognising viral structural antigen expression on the cell membrane 48 h after infection. Reduced HCR was exhibited by radioresistant HeLa cells and by a radiosensitive neuroblastoma cell line, HX142. In contrast, an ataxia telangiectasia cell line, AT5 BIVA, did not show reduced HCR. On the basis of these results we can make no general conclusions about the relevance of HCR to cellular radiosensitivity. We have extended these studies to determine whether our cell lines exhibited enhanced viral reactivation (ER) following a small priming dose of gamma-radiation given to the cells before viral infection. No evidence for this phenomenon was found either in normal or tumour cell lines. PMID:1637659
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Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji
2010-09-01
We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.
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Radiosensitization: enhancing the radiation inactivation of foodborne bacteria
NASA Astrophysics Data System (ADS)
Borsa, J.; Lacroix, M.; Ouattara, B.; Chiasson, F.
2004-09-01
Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D10. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater radiosensitization effect than could be achieved by either factor applied alone. Radiosensitization could be demonstrated with irradiation of either fresh or frozen ground meat. The radiosensitization phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.
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Yang, Lei; Yuan, Xiaopeng; Wang, Jie; Gu, Cheng; Zhang, Haowen; Yu, Jiahua; Liu, Fenju
2015-07-01
The present study aimed to investigate the radiosensitizing effects of tamoxifen (TAM), a non-steroidal anti-estrogen drug, in human glioma A172 and U251 cells in vitro . A colony-forming assay revealed that TAM enhances radiosensitivity in A172 and U251 cells. Treatment with TAM also increased the percentage of apoptotic cells subsequent to ionizing radiation, and increased the expression of apoptotic markers, including cleaved caspase-3 and poly(ADP-ribose) polymerase. Ionizing radiation induced G2/M phase arrest, which was alleviated within 24 h when the radiation-induced DNA damage was repaired. However, flow cytometry analysis revealed that TAM treatment delayed the recovery of cell cycle progression. Additional examination demonstrated that TAM-mediated protein kinase C-ι (PKC-ι) inhibition may lead to the activation of pro-apoptotic B-cell lymphoma 2-associated death promoter, and the dephosphorylation of cyclin-dependent kinase 7, resulting in increased cell apoptosis and sustained G2/M phase arrest following exposure to radiation. The present data indicate that the radiosensitizing effects of TAM on glioma cells are partly due to the inhibition of PKC-ι activity in vitro .
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Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon
2010-01-15
Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression andmore » radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.« less
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NASA Technical Reports Server (NTRS)
1976-01-01
Design concepts for a 1000 mw thermal stationary power plant employing the UF6 fueled gas core breeder reactor are examined. Three design combinations-gaseous UF6 core with a solid matrix blanket, gaseous UF6 core with a liquid blanket, and gaseous UF6 core with a circulating blanket were considered. Results show the gaseous UF6 core with a circulating blanket was best suited to the power plant concept.
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Size-exclusion chromatography using core-shell particles.
Pirok, Bob W J; Breuer, Pascal; Hoppe, Serafine J M; Chitty, Mike; Welch, Emmet; Farkas, Tivadar; van der Wal, Sjoerd; Peters, Ron; Schoenmakers, Peter J
2017-02-24
Size-exclusion chromatography (SEC) is an indispensable technique for the separation of high-molecular-weight analytes and for determining molar-mass distributions. The potential application of SEC as second-dimension separation in comprehensive two-dimensional liquid chromatography demands very short analysis times. Liquid chromatography benefits from the advent of highly efficient core-shell packing materials, but because of the reduced total pore volume these materials have so far not been explored in SEC. The feasibility of using core-shell particles in SEC has been investigated and contemporary core-shell materials were compared with conventional packing materials for SEC. Columns packed with very small core-shell particles showed excellent resolution in specific molar-mass ranges, depending on the pore size. The analysis times were about an order of magnitude shorter than what could be achieved using conventional SEC columns. Copyright © 2016 Elsevier B.V. All rights reserved.
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The high-pressure phase diagram of Fe(0.94)O - A possible constituent of the earth's core
NASA Technical Reports Server (NTRS)
Knittle, Elise; Jeanloz, Raymond
1991-01-01
Electrical resistivity measurements to pressures of 83 GPa and temperatures ranging from 300 K to 4300 K confirm the presence of both crystalline and liquid metallic phases of FeO at pressures above 60-70 GPa and temperatures above 1000 K. By experimentally determinig the melting temperature of FeO to 100 GPa and of a model-core composition at 83 GPa, it is found that the solid-melt equilibria can be described by complete solid solution across the Fe-FeO system at pressures above 70 GPa. The results indicate that oxygen is a viable and likely candidate for the major light alloying element of the earth's liquid outer core. The data suggest that the temperature at the core-mantle boundary is close to 4800 K and that heat lost out of the core accounts for more than 20 percent of the heat flux observed at the surface.
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Annular core liquid-salt cooled reactor with multiple fuel and blanket zones
Peterson, Per F.
2013-05-14
A liquid fluoride salt cooled, high temperature reactor having a reactor vessel with a pebble-bed reactor core. The reactor core comprises a pebble injection inlet located at a bottom end of the reactor core and a pebble defueling outlet located at a top end of the reactor core, an inner reflector, outer reflector, and an annular pebble-bed region disposed in between the inner reflector and outer reflector. The annular pebble-bed region comprises an annular channel configured for receiving pebble fuel at the pebble injection inlet, the pebble fuel comprising a combination of seed and blanket pebbles having a density lower than the coolant such that the pebbles have positive buoyancy and migrate upward in said annular pebble-bed region toward the defueling outlet. The annular pebble-bed region comprises alternating radial layers of seed pebbles and blanket pebbles.
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Optofluidic tuning of multimode interference fiber filters
NASA Astrophysics Data System (ADS)
Antonio-Lopez, J. E.; May-Arrioja, D. A.; LiKamWa, P.
2009-05-01
We report on the optofluidic tuning of MMI-based bandpass filters. It is well known that MMI devices exhibit their highest sensitivity when their diameter (D) is modified, since they have a D2 wavelength dependence. In order to increase the MMF diameter we use a special fiber, called No-Core fiber, which is basically a MMF with a diameter of 125 μm with air as the cover. Therefore, when this No-Core fiber is immersed in liquids with different refractive indexes, as a result of the Goes-Hänchen shift the effective width (fundamental mode width) of the No-Core fiber is increased, and thus the peak wavelength is tuned. A tunability of almost 40 nm in going from air (n=1.333) to ethylene glycol (n=1.434) was easily obtained, with a minimum change in peak transmission, contrast, and bandwidth. Moreover, since replacing the entire liquid can be difficult, the device was placed vertically and the liquid was covering the No-Core fiber in small steps. This provided similar amount of tuning as before, but a more controllable tuning mechanism.
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Imaging and estimating the surface heterogeneity on a droplet containing cosolvents.
Fang, Xiaohua; Li, Bingquan; Wu, Jun; Maldarelli, Charles; Sokolov, Jonathan C; Rafailovich, Miriam H; Somasundaran, Ponisseril
2009-07-23
Cosolvents have numerous applications in many industries as well as scientific research. The shortage in the knowledge of the structures in a cosolvent system is significant. In this work, we display the spatial as well as the kinetic distribution of the cosolvents using droplets as paradigms. When an alcohol/water-containing sessile droplet evaporates on a substrate, it phase segregates into a water-enriched core and a thin alcohol prevailing shell. This is considered to be due to the different escaping rate of solvents out of the liquid-vapor (l-v) interfaces. In between the core and shell phases, there exists a rough and solid-like liquid-liquid (l-l) wall interface as marked by the fluorescent polystyrene spheres and imaged by a confocal microscope. Holes and patches of beads are observed to form on this phase boundary. The water-dispersed beads prefer to partition within the core. The shell prevails in the droplet during most of the drying and shrinks with the l-v boundary. By monitoring the morphological progression of the droplet, the composition of the cosolvent at the liquid-vapor interface is obtained.
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Spaceborne power systems preference analyses. Volume 2: Decision analysis
NASA Technical Reports Server (NTRS)
Smith, J. H.; Feinberg, A.; Miles, R. F., Jr.
1985-01-01
Sixteen alternative spaceborne nuclear power system concepts were ranked using multiattribute decision analysis. The purpose of the ranking was to identify promising concepts for further technology development and the issues associated with such development. Four groups were interviewed to obtain preference. The four groups were: safety, systems definition and design, technology assessment, and mission analysis. The highest ranked systems were the heat-pipe thermoelectric systems, heat-pipe Stirling, in-core thermionic, and liquid-metal thermoelectric systems. The next group contained the liquid-metal Stirling, heat-pipe Alkali Metal Thermoelectric Converter (AMTEC), heat-pipe Brayton, liquid-metal out-of-core thermionic, and heat-pipe Rankine systems. The least preferred systems were the liquid-metal AMTEC, heat-pipe thermophotovoltaic, liquid-metal Brayton and Rankine, and gas-cooled Brayton. The three nonheat-pipe technologies selected matched the top three nonheat-pipe systems ranked by this study.
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Bergquist, Leah; Zhang, Cuiyu; Ribeiro de Almeida, Roberta R.; ...
2017-02-07
Here, we report on the synthesis and characterization of bent-core liquid crystal (LC) compounds and the preparation of mixtures that provide an optically isotropic antiferroelectric (OI-AFLC) liquid crystal display mode over a very wide temperature interval and well below room temperature. From the collection of compounds synthesized during this study, we recognized that several ternary mixtures displayed a modulated SmC aP A phase down to below -40 °C and up to about 100 °C on both heating and cooling, as well as optical tilt angles in the transformed state of approximately 45° (optically isotropic state). The materials were fully characterizedmore » and their liquid crystal as well as electro-optical properties analyzed by polarized optical microscopy, differential scanning calorimetry, synchrotron X-ray diffraction, dielectric spectroscopy, and electro-optical tests.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bergquist, Leah; Zhang, Cuiyu; Ribeiro de Almeida, Roberta R.
Here, we report on the synthesis and characterization of bent-core liquid crystal (LC) compounds and the preparation of mixtures that provide an optically isotropic antiferroelectric (OI-AFLC) liquid crystal display mode over a very wide temperature interval and well below room temperature. From the collection of compounds synthesized during this study, we recognized that several ternary mixtures displayed a modulated SmC aP A phase down to below -40 °C and up to about 100 °C on both heating and cooling, as well as optical tilt angles in the transformed state of approximately 45° (optically isotropic state). The materials were fully characterizedmore » and their liquid crystal as well as electro-optical properties analyzed by polarized optical microscopy, differential scanning calorimetry, synchrotron X-ray diffraction, dielectric spectroscopy, and electro-optical tests.« less
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Two-dimensional liquid chromatography system for online top-down mass spectrometry
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tian, Zhixin; Zhao, Rui; Tolic, Nikola
2010-10-01
An online metal-free weak cation exchange-hydrophilic interaction liquid chromatography/reversed phase liquid chromatography (WCX-HILIC/RPLC) system has been developed for sensitive high-throughput top-down mass spectrometry. Analyzing posttranslational modifications (PTMs) of core histones, with focus on histone H4, tested the system. Using ~24 μg of core histones (H4, H2B, H2A and H3) purified from human fibroblasts, 41 H4 isoforms were identified, with the type and locations of PTMs unambiguously mapped for 20 of these variants. Compared to corresponding offline studies reported previously, online WCXHILIC/ RPLC platform offers significant improvement in sensitivity, with several orders of magnitude reduction in sample requirements and reduction inmore » the overall analysis time. To the best of our knowledge, this study represents the first online two-dimensional (2D) LC-MS/MS characterization of core histone mixture at the intact protein level.« less
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Assembly of metals and nanoparticles into novel nanocomposite superstructures
Xu, Jiaquan; Chen, Lianyi; Choi, Hongseok; Konish, Hiromi; Li, Xiaochun
2013-01-01
Controlled assembly of nanoscale objects into superstructures is of tremendous interests. Many approaches have been developed to fabricate organic-nanoparticle superstructures. However, effective fabrication of inorganic-nanoparticle superstructures (such as nanoparticles linked by metals) remains a difficult challenge. Here we show a novel, general method to assemble metals and nanoparticles rationally into nanocomposite superstructures. Novel metal-nanoparticle superstructures are achieved by self-assembly of liquid metals and nanoparticles in immiscible liquids driven by reduction of free energy. Superstructures with various architectures, such as metal-core/nanoparticle-shell, nanocomposite-core/nanoparticle-shell, network of metal-linked core/shell nanostructures, and network of metal-linked nanoparticles, were successfully fabricated by simply tuning the volume ratio between nanoparticles and liquid metals. Our approach provides a simple, general way for fabrication of numerous metal-nanoparticle superstructures and enables a rational design of these novel superstructures with desired architectures for exciting applications.
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NASA Astrophysics Data System (ADS)
Wu, Wenlan; Li, Junbo; Zou, Sheng; Guo, Jinwu; Zhou, Huiyun
2017-03-01
A method of in-situ reduction to prepare Au@Pt core-satellite nanoparticles (NPs) is described by using Au NPs coating poly[1-methyl 3-(2-methacryloyloxy propylimidazolium bromine)] (PMMPImB-@-Au NPs) as the template. After electrostatic complex chloroplatinic acid with PMMPImB shell, the composite NP was directly reduced with N2H4 to produce Au@Pt core-satellite NPs. The characterization of composite and core-satellite NPs under different amounts of chloroplatinic acid were studied by DLS, UV-vis absorption spectrum and TEM. The satellite Pt NPs with a small size ( 2 nm) dotted around Au core, and the resulting Au@Pt core-satellite NPs showed a red-shift surface plasmon resonance (SPR) and a good dispersion due to effectively electrostatic repulsion providing by the polymeric ionic liquid (PIL) shell. Finally, Au@Pt core-satellite NPs exhibit an enhanced catalytic activity and cycled catalytic capability for the reduction of p-nitrophenol with NaBH4.
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Experimental constraints on light elements in the Earth’s outer core
Zhang, Youjun; Sekine, Toshimori; He, Hongliang; Yu, Yin; Liu, Fusheng; Zhang, Mingjian
2016-01-01
Earth’s outer core is liquid and dominantly composed of iron and nickel (~5–10 wt%). Its density, however, is ~8% lower than that of liquid iron, and requires the presence of a significant amount of light element(s). A good way to specify the light element(s) is a direct comparison of density and sound velocity measurements between seismological data and those of possible candidate compositions at the core conditions. We report the sound velocity measurements of a model core composition in the Fe-Ni-Si system at the outer core conditions by shock-wave experiments. Combining with the previous studies, we found that the best estimate for the outer core’s light elements is ~6 wt% Si, ~2 wt% S, and possible ~1–2.5 wt% O. This composition satisfies the requirements imposed by seismology, geochemistry, and some models of the early core formation. This finding may help us to further constrain the thermal structure of the Earth and the models of Earth’s core formation. PMID:26932596
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Mesomorphic properties of multi-arm chenodeoxycholic acid-derived liquid crystals
NASA Astrophysics Data System (ADS)
Dong, Liang; Yao, Miao; Wu, Shuang-jie; Yao, Dan-Shu; Hu, Jian-She; He, Xiao-zhi; Tian, Mei
2017-12-01
Four multi-arm liquid crystals (LCs) based on chenodeoxycholic acid, termed as 2G-PD, 2G-IB, 2G-BD and 5G-GC, respectively, have been synthesised by convergent method, which nematic LC, 6-(4-((4-ethoxybenzoyl)oxy)phenoxy)-6-oxohexanoic acid, was used as side arm, and chenodeoxycholic acid (CDCA) was used as the first core, 1,2-propanediol (PD), isosorbide (IB), 4,4‧-biphenyldiol (BD) and glucose (GC) were used as the second core, respectively. The first generation product, CDCA2EA, displayed cholesteric phase. The second generation products 2G-BD and 5G-GC displayed cholesteric phase, while 2G-PD and 2G-IB exhibited nematic phase. The multi-arm LC, 2G-IB, did not display cholesteric phase although the two cores were all chiral ones. The result indicated that chirality of the second core sometimes made the multi-arm LCs display nematic phase when cholesteric CDCA-derivative were introduced into the second core. Some attention should be paid on molecular conformation besides the introduction of chiral cores for multi-chiral-core LCs to obtain cholesteric phase.
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NASA Technical Reports Server (NTRS)
Rom, Frank E.
1968-01-01
The three basic types of nuclear power-plants (solid, liquid, and gas core) are compared on the bases of performance potential and the status of current technology. The solid-core systems are expected to have impulses in the range of 850 seconds, any thrust level (as long as it is greater than 10,000 pounds (44,480 newtons)), and thrust-to-engine-weight ratios of 2 to 20 pounds per pound (19.7 to 197 newtons per kilogram). There is negligible or no fuel loss from the solid-core system. The solid-core system, of course, has had the most work done on it. Large-scale tests have been performed on a breadboard engine that has produced specific impulses greater than 700 seconds at thrust levels of about 50,000 pounds (222,000 newtons). The liquid-core reactor would be interesting in the specific impulse range of 1200 to 1500 seconds. Again, any thrust level can be obtained depending on how big or small the reactor is made. The thrust-to-engine weight ratio for these systems would be in the range of 1 to 10. The discouraging feature of the liquid-core system is the high fuel-loss ratio anticipated. Values of 0.01 to 0.1 pound (0.00454 to 0.0454 kilograms) or uranium loss per pound (0.454 kilograms) of hydrogen are expected, if impulses in the range of 1200 to 1500 seconds are desired. The gas-core reactor shows specific impulses in the range of 1500 to 2500 seconds. The thrust levels should be at least as high as the weight so that the thrust-to-weight ratio does not go below 1. Because the engine weight is not expected to be under 100,000 pounds (444,800 newtons), thrust levels higher than 100,000 pounds (448,000 newtons) are of interest. The thrust-to-engine weights, in that case, would run from 1 to 20 pounds per pound (9.8 to 19.7 kilograms). Gas-core reactors tend to be very large, and can have high thrust-to-weight ratios. As in the case of the liquid-core system, the fuel loss that will be attendant with gas cores as envisioned today will be rather high. The loss rates will be 0.01 to 0.1 pound of uranium (0.00454 to 0.0454 kilograms) for each pound (0.454 kilograms) of hydrogen.
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Influence of a Fluid Lunar Core on the Moons Orientation
NASA Technical Reports Server (NTRS)
Williams, J. G.; Boggs, D. H.; Ratcliff, J. T.; Yoder, C. F.; Dickey, J. O.
2001-01-01
Oblateness of and dissipation at the lunar liquid-core/solid-mantle boundary affects the precession of core and mantle. Analysis of Lunar Laser ranges gives a weak detection of oblateness and a strong determination of dissipation. Additional information is contained in the original extended abstract.
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Ye, Jing; Cao, Xiaoji; Cheng, Zhuo; Qin, Ye; Lu, Yanbin
2015-12-01
In this work, the chromatographic performance of superficially porous particles (Halo core-shell C18 column, 50 mm × 2.1 mm, 2.7 μm) was compared with that of sub-2 μm fully porous particles (Acquity BEH C18 , 50 mm × 2.1 mm, 1.7 μm). Four parabens, methylparaben, ethylparaben, propylparaben, and butylparaben, were used as representative compounds for calculating the plate heights in a wide flow rate range and analyzed on the basis of the Van Deemter and Knox equations. Theoretical Poppe plots were constructed for each column to compare their kinetic performance. Both phases gave similar minimum plate heights when using nonreduced coordinates. Meanwhile, the flat C-term of the core-shell column provided the possibilities for applying high flow rates without significant loss in efficiency. The low backpressure of core-shell particles allowed this kind of column, especially compatible with conventional high-performance liquid chromatography systems. Based on these factors, a simple high-performance liquid chromatography method was established and validated for the determination of parabens in various seafood sauces using the Halo core-shell C18 column for separation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Liquid uranium alloy-helium fission reactor
Minkov, Vladimir
1986-01-01
This invention teaches a nuclear fission reactor having a core vessel and at least one tandem heat exchanger vessel coupled therewith across upper and lower passages to define a closed flow loop. Nuclear fuel such as a uranium alloy in its liquid phase fills these vessels and flow passages. Solid control elements in the reactor core vessel are adapted to be adjusted relative to one another to control fission reaction of the liquid fuel therein. Moderator elements in the other vessel and flow passages preclude fission reaction therein. An inert gas such as helium is bubbled upwardly through the heat exchanger vessel operable to move the liquid fuel upwardly therein and unidirectionally around the closed loop and downwardly through the core vessel. This helium gas is further directed to heat conversion means outside of the reactor vessels to utilize the heat from the fission reaction to generate useful output. The nuclear fuel operates in the 1200.degree.-1800.degree. C. range, and even higher to 2500.degree. C., limited only by the thermal effectiveness of the structural materials, increasing the efficiency of power generation from the normal 30-35% with 300.degree.-500.degree. C. upper limit temperature to 50-65%. Irradiation of the circulating liquid fuel, as contrasted to only localized irradiation of a solid fuel, provides improved fuel utilization.
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Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying
2012-06-01
The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.
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Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions.
Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M; Ricoul, Michelle; Sabatier, Laure
2016-01-01
Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy.
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Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions
Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M.; Ricoul, Michelle; Sabatier, Laure
2016-01-01
Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term “relative dose effect” (RDE). This ratio is advantageous, as it allows for simple comparison of dose–response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2–15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy. PMID:27379201
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NASA Astrophysics Data System (ADS)
Lagerwall, Jan P. F.
2012-03-01
"Wearable technology" or "smart textiles" are concepts that are very rapidly gaining in attention around the world, as industry as well as academia are making major advances in integrating advanced devices with various textiles around our household. The technological challenges involved in this development are however considerable, calling for new solutions, new materials and truly original thinking. An attractive approach to realize certain classes of wearable devices may be to use textile fibers functionalized by responsive materials such as liquid crystals, normally not connected to textiles. We can produce non-woven textiles with such fibers by means of electrospinning, a technique for producing very thin polymer fibers that can be uniform or with core-sheath geometries. Since the core can be made out of traditionally non-spinnable materials we can use coaxial electrospinning (one fluid spun inside another) to produce composite fibers with a core of liquid crystal inside a polymer sheath. The resulting fibers constitute an entirely new configuration for applying liquid crystals, giving the fibers functionality and responsiveness. For instance, with a cholesteric core we can produce non-woven mats with iridescent color that can be tuned (or removed) e.g. by heating or cooling. In this paper I describe our method of producing these novel functionalized fibers and their characterization, and I will discuss the directions for future research and application possibilities, e.g. in clothing-integrated sensors and indicators.
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The chemical composition of the cores of the terrestrial planets and the moon
NASA Technical Reports Server (NTRS)
Kuskov, O. L.; Khitarov, N. I.
1977-01-01
Using models of the quasi-chemical theory of solutions, the activity coefficients of silicon are calculated in the melts Fe-Si, Ni-Si, and Fe-Ni-Si. The calculated free energies of solution of liquid nickel and silicon in liquid iron in the interval 0 to 1400 kbar and 1500 to 4000 K, shows that Fe-Ni-Si alloy is stable under the conditions of the outer core of the earth and the cores of the terrestrial planets. The oxidation-reduction conditions are studied, and the fugacity of oxygen in the mantles of the planets and at the core-mantle boundary are calculated. The mechanism of reduction of silicon is analyzed over a broad interval of p and T. The interaction between the matter of the core and mantle is studied, resulting in the extraction of silicon from the mantle and its solution in the material of the core. It is concluded that silicon can enter into the composition of the outer core of the earth and Venus, but probably does not enter into the composition of the cores of Mercury, Mars, and the moon, if in fact the latter possesses one.
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Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells.
Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh
2017-03-28
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.
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Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.
Hamada, Nobuyuki
2017-10-01
In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.
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Ruiz de Almodóvar, José Mariano; Guirado, Damian; Isabel Núñez, María; López, Escarlata; Guerrero, Rosario; Valenzuela, María Teresa; Villalobos, Mercedes; del Moral, Rosario
2002-03-01
The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities. Radiosensitivity (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp). The existence of an inter-individual variation in the parameter (x) is described through the range (0.40-4.72 dsb/Gy/DNA unit) of values found, which have been fitted to the mathematical model defined by the log-normal distribution (mu = 0.42+/-0.03; sigma = 0.52+/-0.03; R(2)=0.9475). A total of 189 patients received radiotherapy after surgical treatment. Among them, we have detected 15 patients who developed severe skin reactions and we have compared their radiosensitivity values with the rest of patients treated. Our results suggest that DNA initial damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. Values of x higher than 3.20 dsb/Gy/DNA unit theoretically should correspond to the highly radio-sensitive patients. Using the experimental results, we have calculated the strength of the test by means of the area under the receiver operator characteristic curves (A(Z)) to determine whether the radiosensitivity assay can discriminate between patients according to their radiation response. The value found (A(Z)=0.675+/-0.072) is indicative of a fair-poor discriminating capacity of the test to identify the patients with higher risk of developing a severe acute reaction during the radiotherapy treatment.
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SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Garcia, L; Tambasco, M
2016-06-15
Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity.more » Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.« less
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Cho, Hang Joo; Kim, Sin Young; Kim, Kee Hwan; Kang, Won Kyung; Kim, Ji Il; Oh, Seong Tack; Kim, Jeong Soo; An, Chang Hyeok
2009-05-21
The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines. In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods. After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines. In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.
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Timme, Cindy R; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J
2018-06-01
Radiotherapy is a primary treatment modality for glioblastomas (GBM). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSB), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation. In a similar concentration-dependent manner, VX-984 treatment enhanced the radiosensitivity of each GBM cell line as defined by clonogenic analysis. As determined by γH2AX expression and neutral comet analyses, VX-984 inhibited the repair of radiation-induced DNA double-strand break in U251 and NSC11 GBM cells, suggesting that the VX-984-induced radiosensitization is mediated by an inhibition of DNA repair. Extending these results to an in vivo model, treatment of mice with VX-984 inhibited radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts, indicating that this compound crosses the blood-brain tumor barrier at sufficient concentrations. For mice bearing U251 or NSC11 brain tumors, VX-984 treatment alone had no significant effect on overall survival; radiation alone increased survival. The survival of mice receiving the combination protocol was significantly increased as compared with control and as compared with radiation alone. These results indicate that VX-984 enhances the radiosensitivity of brain tumor xenografts and suggest that it may be of benefit in the therapeutic management of GBM. Mol Cancer Ther; 17(6); 1207-16. ©2018 AACR . ©2018 American Association for Cancer Research.
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Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling.
Nambiar, Dhanya K; Rajamani, Paulraj; Deep, Gagan; Jain, Anil K; Agarwal, Rajesh; Singh, Rana P
2015-12-01
Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective radiosensitizer, we studied the radiosensitizing effects and associated mechanisms of silibinin in prostate cancer. The radiosensitizing effect of silibinin with ionizing radiation (IR) was assessed on radioresistant prostate cancer cell lines by clonogenic, cell cycle, cell death, and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μmol/L) enhanced IR (2.5-10 Gy)-caused inhibition (up to 96%, P < 0.001) of colony formation selectively in prostate cancer cells, and prolonged and enhanced IR-caused G2-M arrest, apoptosis, and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/2) and EGFR signaling and attenuated the levels of antiapoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H2AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly radiosensitized DU145 tumor xenograft inhibition (84%, P < 0.01) with higher apoptotic response (10-fold, P < 0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced prosurvival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Because silibinin is already in phase II clinical trial for prostate cancer patients, the present finding has translational relevance for radioresistant prostate cancer. ©2015 American Association for Cancer Research.
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Shinohara, Eric T; Geng, Ling; Tan, Jiahui; Chen, Heidi; Shir, Yu; Edwards, Eric; Halbrook, James; Kesicki, Edward A; Kashishian, Adam; Hallahan, Dennis E
2005-06-15
DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.
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Cui, Jie; Xu, Xin; Yang, Mo; Chen, Chen; Zhao, Wei; Wu, Mei; Zhang, Zun-zhen
2011-11-01
To explore the relationship between the expression level of DNA polymerase beta (pol beta) and 60Co gamma-ray radiosensitivity and provide a basis on improving the efficiency of radiotherapy theoretically. pol beta wild-type cells (pol beta +/+), pol beta null cells (pol beta -/-) and pol beta overexpressed cells (polp beta oe) were applied as a model system. The radiosensitivity of 60Co gamma-ray on the cell was detected by MTT assay and clone formation assay. The DCFH-DA fluorescent probe was used to examine the cellular ROS after 60Co gamma-rays radiation. MTT assay showed that after radiation by 60Co gamma-rays followed with 72 h incubation, the cell viabilities in the three kinds of cells decreased significantly with a dose-response relationship (r-/+ = -0.976, r-/- = -0.977, r(oe) = -0.982, P<0.05). In addition, the viability of pol beta -/- cell was lower than those of other two kinds of cells at the same dose (P<0.05). Likewise, the colony number and colony formation rate in all tested cells also decreased after exposure to 60Co gamma-rays. The ROS level in the three kinds of cells was enhanced after treatment with 60Co gamma-ray, and the ROS level in pol beta -/- cells was much higher than that in the other two kinds of cells (P<0.05). Cell death caused by 60Co gamma-ray may associated with the DNA oxidative damage mediated by ROS; Overexpression of pol beta could protect against oxidative DNA damage, thus the cell apoptosis/death, thereby leading to reducing the radiosensitivity of 60Co gamma-rays, while null of DNA pol beta could increase radiosensitivity of 60Co gamma-rays by compromising the DNA repair.
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NASA Astrophysics Data System (ADS)
Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.
2011-03-01
Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.
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Fu, Yonghong; Zhang, Sen; Wang, Dongjie; Wang, Jing
2018-05-16
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed. Cell apoptosis was also analyzed by flow cytometry, while western blotting was performed to examine the activation of EGFR and its downstream kinases in H1650 cells after Icotinib and radiation treatment. Furthermore, a xenograft animal model was established to evaluate the radiosensitivity of Icotinib in vivo and to confirm its mechanism. Our results demonstrate that pretreatment with Icotinib reduced clonogenic survival after radiation, inhibited EGFR activation, and increased radiation-induced apoptosis in H1650 cells. The phosphorylation of protein kinase B (AKT), extracellular regulated protein kinase 1/2 (ERK1/2), and EGFR was inhibited after Icotinib and radiation combination treatment in vitro and in vivo compared with individual treatments. Combination treatment also affected the expression of the DNA repair protein H2A histone family member X (γ-H2AX). In conclusion, our results reveal that Icotinib enhances radiosensitivity in lung cancers in vitro and in vivo and the mechanism of this may involve blocking the EGFR-AKT and MAPK-ERK pathways and limiting DNA repair. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Huang, Xiaomin; Liu, Ting; Wang, Qiongyao; Zhu, Weiliang; Meng, Hui; Guo, Linlang; Wei, Ting; Zhang, Jian
2017-05-23
N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyses the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. Subsequently, we further explored the signalling downstream of EGF, particularly the PI3K/Akt signalling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumour growth. In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Jayakumar, Sundarraj; Kunwar, Amit; Sandur, Santosh K; Pandey, Badri N; Chaubey, Ramesh C
2014-01-01
Radioresistance is the major impediment in radiotherapy of many cancers including prostate cancer, necessitating the need to understand the factors contributing to radioresistance in tumor cells. In the present study, the role of cellular redox and redox sensitive transcription factor, Nrf2 in the radiosensitivity of prostate cancer cell lines PC3 and DU145, has been investigated. Differential radiosensitivity of PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. Their redox status was measured using DCFDA and DHR probes. Expression of Nrf2 and its dependent genes was measured by EMSA and real time PCR. Knockdown studies were done using shRNA transfection. PC3 and DU145 cells differed significantly in their radiosensitivity as observed by clonogenic survival, apoptosis and neutral comet assays. Both basal and inducible levels of ROS were higher in PC3 cells than that of DU145 cells. DU145 cells showed higher level of basal GSH content and GSH/GSSG ratio than that of PC3 cells. Further, significant increase in both basal and induced levels of Nrf2 and its dependent genes was observed in DU145 cells. Knock-down experiments and pharmacological intervention studies revealed the involvement of Nrf2 in differential radio-resistance of these cells. Cellular redox status and Nrf2 levels play a causal role in radio-resistance of prostate cancer cells. The pivotal role Nrf2 has been shown in the radioresistance of tumor cells and this study will further help in exploiting this factor in radiosensitization of other tumor cell types. © 2013.
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Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hung, Shih-Kai; Department of Radiation Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan; Tzu Chi University School of Medicine, Hualian, Taiwan
2010-07-15
Purpose: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. Methods and Materials: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-{kappa}B) and Akt inmore » andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. Results: Concurrent andrographolide treatment (10 {mu}M, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 {+-} 2.5 days) compared with radiation alone (22 {+-} 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-{kappa}B activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-{kappa}B activity. Conclusion: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-{kappa}B activity. These observations indicate that andrographolide is a novel radiosensitizing agent with potential application in cancer radiotherapy.« less
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40 CFR 264.278 - Unsaturated zone monitoring.
Code of Federal Regulations, 2011 CFR
2011-07-01
... or operator must monitor the soil and soil-pore liquid to determine whether hazardous constituents... unsaturated zone monitoring system that includes soil monitoring using soil cores and soil-pore liquid... the quality of background soil-pore liquid quality and the chemical make-up of soil that has not been...
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40 CFR 264.278 - Unsaturated zone monitoring.
Code of Federal Regulations, 2014 CFR
2014-07-01
... or operator must monitor the soil and soil-pore liquid to determine whether hazardous constituents... unsaturated zone monitoring system that includes soil monitoring using soil cores and soil-pore liquid... the quality of background soil-pore liquid quality and the chemical make-up of soil that has not been...
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40 CFR 264.278 - Unsaturated zone monitoring.
Code of Federal Regulations, 2012 CFR
2012-07-01
... or operator must monitor the soil and soil-pore liquid to determine whether hazardous constituents... unsaturated zone monitoring system that includes soil monitoring using soil cores and soil-pore liquid... the quality of background soil-pore liquid quality and the chemical make-up of soil that has not been...
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40 CFR 264.278 - Unsaturated zone monitoring.
Code of Federal Regulations, 2013 CFR
2013-07-01
... or operator must monitor the soil and soil-pore liquid to determine whether hazardous constituents... unsaturated zone monitoring system that includes soil monitoring using soil cores and soil-pore liquid... the quality of background soil-pore liquid quality and the chemical make-up of soil that has not been...
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40 CFR 264.278 - Unsaturated zone monitoring.
Code of Federal Regulations, 2010 CFR
2010-07-01
... or operator must monitor the soil and soil-pore liquid to determine whether hazardous constituents... unsaturated zone monitoring system that includes soil monitoring using soil cores and soil-pore liquid... the quality of background soil-pore liquid quality and the chemical make-up of soil that has not been...
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A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse
NASA Technical Reports Server (NTRS)
Okayasu, R.; Suetomi, K.; Yu, Y.; Silver, A.; Bedford, J. S.; Cox, R.; Ullrich, R. L.
2000-01-01
We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.
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NASA Technical Reports Server (NTRS)
Wu, H.; George, K.; Willingham, V.; Cucinotta, F. A.
2001-01-01
If radiosensitivity is altered in a microgravity environment, it will affect the accuracy of assessing astronauts' risk from exposure to space radiation. To investigate the effects of space flight on radiosensitivity, we exposed a crewmember's blood to gamma rays at doses ranging from 0 to 3 Gy and analyzed chromosome aberrations in mitotic lymphocytes. The blood samples were collected 10 days prior to an 8-day Shuttle mission, the day the flight returned, and 14 days after the flight. After exposure, lymphocytes were stimulated to grow in media containing phytohaemagglutinin (PHA) and mitotic cells were harvested for chromosome analysis using a fluorescence in situ hybridization (FISH) with whole chromosome specific probes. The dose response of total exchanges showed no changes in the radiosensitivity after the mission.
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The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors
NASA Astrophysics Data System (ADS)
Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier
2016-07-01
We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.
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NASA Astrophysics Data System (ADS)
Date, Kumi; Ishigure, Takaaki
2017-02-01
Polymer optical waveguides with graded-index (GI) circular cores are fabricated using the Mosquito method, in which the positions of parallel cores are accurately controlled. Such an accurate arrangement is of great importance for a high optical coupling efficiency with other optical components such as fiber ribbons. In the Mosquito method that we developed, a core monomer with a viscous liquid state is dispensed into another liquid state monomer for cladding via a syringe needle. Hence, the core positions are likely to shift during or after the dispensing process due to several factors. We investigate the factors, specifically affecting the core height. When the core and cladding monomers are selected appropriately, the effect of the gravity could be negligible, so the core height is maintained uniform, resulting in accurate core heights. The height variance is controlled in +/-2 micrometers for the 12 cores. Meanwhile, larger shift in the core height is observed when the needle-tip position is apart from the substrate surface. One of the possible reasons of the needle-tip height dependence is the asymmetric volume contraction during the monomer curing. We find a linear relationship between the original needle-tip height and the core-height observed. This relationship is implemented in the needle-scan program to stabilize the core height in different layers. Finally, the core heights are accurately controlled even if the cores are aligned on various heights. These results indicate that the Mosquito method enables to fabricate waveguides in which the cores are 3-dimensionally aligned with a high position accuracy.
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Xiong, Kai; Shao, Li Hong; Zhang, Hai Qin; Jin, Linlin; Wei, Wei; Dong, Zhuo; Zhu, Yue Quan; Wu, Ning; Jin, Shun Zi; Xue, Li Xiang
2018-03-01
Radiotherapy is commonly used to treat lung cancer but may not kill all cancer cells, which may be attributed to the radiotherapy resistance that often occurs in non-small cell lung cancer (NSCLC). At present, the molecular mechanism of radio-resistance remains unclear. Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF), was demonstrated to be associated with radio-resistance of NSCLC cells via the VEGF-phosphoinositide 3-kinase-nuclear factor-κB pathway in our previous study. It was hypothesized that certain microRNAs (miRs) may serve crucial functions in radio-sensitivity by regulating NRP1. Bioinformatics predicted that NRP1 was a potential target of miR-9, and this was validated by luciferase reporter assays. Functionally, miR-9-transfected A549 cells exhibited a decreased proliferation rate, increased apoptosis rate and attenuated migratory and invasive abilities. Additionally, a high expression of miR-9 also significantly enhanced the radio-sensitivity of A549 cells in vitro and in vivo . These data improve understanding of the mechanisms of cell radio-resistance, and suggest that miR-9 may be a molecular target for the prediction of radio-sensitivity in NSCLC.
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Song, Lili; Liu, Shikai; Zeng, Saitian; Zhang, Liang; Li, Xia
2015-07-30
Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer. qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models. The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis. The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.
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GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level.
Li, Qing; Wei, Xi; Zhou, Zhi-Wei; Wang, Shu-Nan; Jin, Hua; Chen, Kui-Jun; Luo, Jia; Westover, Kenneth D; Wang, Jian-Min; Wang, Dong; Xu, Cheng-Xiong; Shan, Jin-Lu
2018-05-09
Radioresistance remains a major clinical challenge in cervical cancer therapy. However, the mechanism for the development of radioresistance in cervical cancer is unclear. Herein, we determined that growth arrest and DNA-damage-inducible protein 45α (GADD45α) is decreased in radioresistant cervical cancer compared to radiosensitive cancer both in vitro and in vivo. In addition, silencing GADD45α prevents cervical cancer cells from undergoing radiation-induced DNA damage, cell cycle arrest, and apoptosis. More importantly, our data show that the overexpression of GADD45α significantly enhances the radiosensitivity of radioresistant cervical cancer cells. These data show that GADD45α decreases the cytoplasmic distribution of APE1, thereby enhancing the radiosensitivity of cervical cancer cells. Furthermore, we show that GADD45α inhibits the production of nitric oxide (NO), a nuclear APE1 export stimulator, by suppressing both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in cervical cancer cells. In conclusion, our findings suggest that decreased GADD45α expression significantly contributes to the development of radioresistance and that ectopic expression of GADD45α sensitizes cervical cancer cells to radiotherapy. GADD45α inhibits the NO-regulated cytoplasmic localization of APE1 through inhibiting eNOS and iNOS, thereby enhancing the radiosensitivity of cervical cancer cells.
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Platinum Partitioning at Low Oxygen Fugacity: Implications for Core Formation Processes
NASA Technical Reports Server (NTRS)
Medard, E.; Martin, A. M.; Righter, K.; Lanziroti, A.; Newville, M.
2016-01-01
Highly siderophile elements (HSE = Au, Re, and the Pt-group elements) are tracers of silicate / metal interactions during planetary processes. Since most core-formation models involve some state of equilibrium between liquid silicate and liquid metal, understanding the partioning of highly siderophile elements (HSE) between silicate and metallic melts is a key issue for models of core / mantle equilibria and for core formation scenarios. However, partitioning models for HSE are still inaccurate due to the lack of sufficient experimental constraints to describe the variations of partitioning with key variable like temperature, pressure, and oxygen fugacity. In this abstract, we describe a self-consistent set of experiments aimed at determining the valence of platinum, one of the HSE, in silicate melts. This is a key information required to parameterize the evolution of platinum partitioning with oxygen fugacity.
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Highly siderophile elements were stripped from Earth’s mantle by iron sulfide segregation
NASA Astrophysics Data System (ADS)
Rubie, David C.; Laurenz, Vera; Jacobson, Seth A.; Morbidelli, Alessandro; Palme, Herbert; Vogel, Antje K.; Frost, Daniel J.
2016-09-01
Highly siderophile elements (HSEs) are strongly depleted in the bulk silicate Earth (BSE) but are present in near-chondritic relative abundances. The conventional explanation is that the HSEs were stripped from the mantle by the segregation of metal during core formation but were added back in near-chondritic proportions by late accretion, after core formation had ceased. Here we show that metal-silicate equilibration and segregation during Earth’s core formation actually increased HSE mantle concentrations because HSE partition coefficients are relatively low at the high pressures of core formation within Earth. The pervasive exsolution and segregation of iron sulfide liquid from silicate liquid (the “Hadean matte”) stripped magma oceans of HSEs during cooling and crystallization, before late accretion, and resulted in slightly suprachondritic palladium/iridium and ruthenium/iridium ratios.
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The Earth's core composition from high pressure density measurements of liquid iron alloys
NASA Astrophysics Data System (ADS)
Morard, G.; Siebert, J.; Andrault, D.; Guignot, N.; Garbarino, G.; Guyot, F.; Antonangeli, D.
2013-07-01
High-pressure, high-temperature in situ X-ray diffraction has been measured in liquid iron alloys (Fe-5 wt% Ni-12 wt% S and Fe-5 wt% Ni-15 wt% Si) up to 94 GPa and 3200 K in laser-heated diamond anvil cells. From the analysis of the X-ray diffuse scattering signal of the metallic liquids, we determined density and bulk modulus of the two liquid alloys. Comparison with a reference Earth model indicates that a core composition containing 6% of sulfur and 2% of silicon by weight would best match the geophysical data. Models with 2.5% of sulfur and 4-5% of silicon are still consistent with geophysical constraints whereas silicon only compositions are not. These results suggest only moderate depletion of sulfur in the bulk Earth.
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Apparatus for detecting leakage of liquid sodium
Himeno, Yoshiaki
1978-01-01
An apparatus for detecting the leakage of liquid sodium includes a cable-like sensor adapted to be secured to a wall of piping or other equipment having sodium on the opposite side of the wall, and the sensor includes a core wire electrically connected to the wall through a leak current detector and a power source. An accidental leakage of the liquid sodium causes the corrosion of a metallic layer and an insulative layer of the sensor by products resulted from a reaction of sodium with water or oxygen in the atmospheric air so as to decrease the resistance between the core wire and the wall. Thus, the leakage is detected as an increase in the leaking electrical current. The apparatus is especially adapted for use in detecting the leakage of liquid sodium from sodium-conveying pipes or equipment in a fast breeder reactor.
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Europa's differentiated internal structure: inferences from four Galileo encounters.
Anderson, J D; Schubert, G; Jacobson, R A; Lau, E L; Moore, W B; Sjogren, W L
1998-09-25
Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius. The thickness of Europa's outer shell of water ice-liquid must lie in the range of about 80 to 170 kilometers.
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Inferences from the dynamical history of Mercury's rotation
NASA Technical Reports Server (NTRS)
Peale, S. J.
1976-01-01
The history of Mercury's spin angular momentum is reviewed. It is shown that the current nonsynchronous but resonant spin and the nearly zero obliquity place almost no restrictions on the primordial spin state. The only exception comes about from a liquid core-solid mantle interaction which excludes a slow primordial spin concurrent with a large obliquity. The current occupancy of a final evolutionary spin state leads to the description of a scheme by which we can determine the extent of a currently liquid Mercurian core.
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NASA Astrophysics Data System (ADS)
Shi, Chao; Zhang, Yi; Gu, Claire; Seballos, Leo; Zhang, Jin Z.
2008-02-01
This work demonstrates the use of a highly sensitive Liquid Core Photonic Crystal Fiber (LCPCF) Surface Enhanced Raman Scattering (SERS) sensor in detecting biological and biochemical molecules. The Photonic Crystal Fiber (PCF) probe was prepared by carefully sealing the cladding holes using a fusion splicer while leaving the central hollow core open, which ensures that the liquid mixture of the analyte and silver nanoparticles only fills in the hollow core of the PCF, therefore preserving the photonic bandgap. The dependence of the SERS signal on the excitation power and sample concentration was fully characterized using Rhodamine 6G (R6G) molecules. The result shows that the LCPCF sensor has significant advantages over flat surface SERS detections at lower concentrations. This is attributed to the lower absorption at lower concentration leading to a longer effective interaction length inside the LCPCF, which in turn, results in a stronger SERS signal. Several biomolecules, such as Prostate Specific Antigen (PSA) and alpha-synuclein, which are indicators of prostate cancer and Parkinson's disease, respectively, and fail to be detected directly, are successfully detected by the LCPCF sensor. Our results demonstrate the potential of the LCPCF SERS sensor for biomedical detection at low concentrations.
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Bertorelle, Franck; Russier-Antoine, Isabelle; Calin, Nathalie; Comby-Zerbino, Clothilde; Bensalah-Ledoux, Amina; Guy, Stephan; Dugourd, Philippe; Brevet, Pierre-François; Sanader, Željka; Krstić, Marjan; Bonačić-Koutecký, Vlasta; Antoine, Rodolphe
2017-05-04
We report facile synthesis of the Au 10 (SG) 10 nanoclusters, where SG stands for glutathione, found to be promising as a new class of radiosensitizers for cancer radiotherapy. The homoleptic catenane structure with two Au 5 SG 5 interconnected rings, among different isomer structures, gives the best agreement between theoretical and experimental optical spectra and XRD patterns. This catenane structure exhibits a centrosymmetry-broken structure, resulting in enhanced second harmonic response and new characteristic circular dichroism signals in the spectral region of 250-400 nm. This is the first determination of the nonlinear optical properties of a ligated cluster with an equal Au-to-ligand ratio, thus without a metallic core and therefore zero confined electrons. Insight into the nonlinear and chiroptical efficiencies arising from interplay between structural and electronic properties is provided by the TD-DFT approach.
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Torsional Oscillations of the Earths's Core
NASA Technical Reports Server (NTRS)
Hide, Raymond; Boggs, Dale H.; Dickey, Jean O.
1997-01-01
Torsional oscillations of the Earth's liquid metallic outer core are investigated by diving the core into twenty imaginary e1qui-volume annuli coaxial with the axis of ratation of the Earth and determining temproal fluctuations in the axial component of angular memonetum of each annulus under the assumption of iso-rotation on cylindrical surfaces.
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Solubility of K in Fe-S liquid, silicate-K/Fe-S/liq equilibria, and their planetary implications
NASA Technical Reports Server (NTRS)
Gangully, J.; Kennedy, G. C.
1977-01-01
Potassium has been found to have extremely limited absolute solubility in Fe-S liquid in the pressure-temperature range of 18 to 40 kbars, 1050 to 1150 C, and fO2 within the field of metallic iron. It also partitioned into a certain silicate phase highly in preference to Fe-S liquid at 30 kbar and 1100 C. The dependence of the partitioning of K between solid silicate and Fe-S liquid on fO2 and compositions of mineral solid solutions have been analyzed. These experimental data, along with those of others, limit the amount of K that could fractionate in Fe-S liquid layers or a core in the early history of the moon and, thus, act as localized heat sources in its thermal history models; the data also seem to argue against a chondritic abundance of potassium for earth. The question of fractionation of enough K-40 in an Fe-S liquid outer core of earth to provide the necesary thermal energy for the geomagnetic dynamo remains unresolved.
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Modeling the structure and thermodynamics of ferrocenium-based ionic liquids.
Bernardes, Carlos E S; Mochida, Tomoyuki; Canongia Lopes, José N
2015-04-21
A new force-field for the description of ferrocenium-based ionic liquids is reported. The proposed model was validated by confronting Molecular Dynamics simulations results with available experimental data-enthalpy of fusion, crystalline structure and liquid density-for a series of 1-alkyl-2,3,4,5,6,7,8,9-octamethylferrocenium bis(trifluoromethylsulfonyl)imide ionic liquids, [CnFc][NTf2] (3 ≤ n ≤ 10). The model is able to reproduce the densities and enthalpies of fusion with deviations smaller than 2.6% and 4.8 kJ mol(-1), respectively. The MD simulation trajectories were also used to compute relevant structural information for the different [CnFc][NTf2] ionic liquids. The results show that, unlike other ILs, the alkyl side chains present in the cations are able to interact directly with the ferrocenium core of other ions. Even the ferrocenium charged cores (with relatively mild charge densities) are able to form small contact aggregates. This causes the partial rupture of the polar network and precludes the formation of extended nano-segregated polar-nonpolar domains normally observed in other ionic liquids.
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Nondestructive Evaluation Methods for the Ares I Common Bulkhead
NASA Technical Reports Server (NTRS)
Walker, James
2010-01-01
A large scale bonding demonstration test article was fabricated to prove out manufacturing techniques for the current design of the NASA Ares I Upper Stage common bulkhead. The common bulkhead serves as the single interface between the liquid hydrogen and liquid oxygen portions of the Upper Stage propellant tank. The bulkhead consists of spin-formed aluminum domes friction stir welded to Y-rings and bonded to a perforated phenolic honeycomb core. Nondestructive evaluation methods are being developed for assessing core integrity and the core-to-dome bond line of the common bulkhead. Detection of manufacturing defects such as delaminations between the core and face sheets as well as service life defects such as crushed or sheared core resulting from impact loading are all of interest. The focus of this work will be on the application of thermographic, shearographic, and phased array ultrasonic methods to the bonding demonstration article as well as various smaller test panels featuring design specific defect types and geometric features.
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NASA Astrophysics Data System (ADS)
Porsezian, K.; Nithyanandan, K.; Vasantha Jayakantha Raja, R.; Ganapathy, R.
2013-07-01
The supercontinuum generation (SCG) in liquid core photonic crystal fiber (LCPCF) with versatile nonlinear response and the spectral broadening in dual core optical fiber is presented. The analysis is presented in two phase, phase I deals with the SCG in LCPCF with the effect of saturable nonlinearity and re-orientational nonlinearity. We identify and discuss the generic nature of the saturable nonlinearity and reorientational nonlinearity in the SCG, using suitable model. For the physical explanation, modulational instability and soliton fission techniques is implemented to investigate the impact of saturable nonlinear response and slow nonlinear response, respectively. It is observed that the saturable nonlinearity inevitably suppresses the MI and the subsequent SCG. On the other hand, the re-orientational nonlinearity contributes to the slow nonlinear response in addition to the conventional fast response due to the electronic contribution. The phase II features the exclusive investigation of the spectral broadening in the dual core optical fiber.
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Core dynamics and the nutations of the Earth.
NASA Astrophysics Data System (ADS)
Dehant, V. M. A.; Laguerre, R.; Rekier, J.; Rivoldini, A.; Trinh, A.; Triana, A. S.; Van Hoolst, T.; Zhu, P.
2016-12-01
We here present an overview of the recent activities within the project RotaNut - Rotation and Nutation of a Wobbly Earth, an ERC Advanced Grant funding from the European Research Council. We have recomputed the Basic Earth Parameters from recent VLBI series and we interpret them in terms of physics of the Earth's deep interior. This includes updates of the nutational constraints on Earth's internal magnetic field and inner core viscosity, as well as of the coupling constants at the core-mantle boundary (CMB) and inner core boundary ICB. We have explored on simplified Earth models the interactions between rotational and gravito-inertial modes. With the help of numerical simulations, we have also addressed the coupling between the global rotation and the inertial waves in the fluid core through parametric instabilities. Special interests have been given to the influence of the inner core onto the stability properties of the liquid core and the large scale formation in the turbulent flow through inverse cascade of energy. The role of precession and nutation forcing for the liquid core is characterized as well as the interaction between the Free Core Nutation (in the fluid core community called the tilt-over mode) and the inertial waves. This research represents the first steps in the project RotaNut financed by the European Research Council under ERC Advanced Grant 670874 for 2015-2020.
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Roesler, Erika L.; Posselt, Derek J.; Rood, Richard B.
2017-04-06
Three-dimensional large eddy simulations (LES) are used to analyze a springtime Arctic mixed-phase stratocumulus observed on 26 April 2008 during the Indirect and Semi-Direct Aerosol Campaign. Two subgrid-scale turbulence parameterizations are compared. The first scheme is a 1.5-order turbulent kinetic energy (1.5-TKE) parameterization that has been previously applied to boundary layer cloud simulations. The second scheme, Cloud Layers Unified By Binormals (CLUBB), provides higher-order turbulent closure with scale awareness. The simulations, in comparisons with observations, show that both schemes produce the liquid profiles within measurement variability but underpredict ice water mass and overpredict ice number concentration. The simulation using CLUBBmore » underpredicted liquid water path more than the simulation using the 1.5-TKE scheme, so the turbulent length scale and horizontal grid box size were increased to increase liquid water path and reduce dissipative energy. The LES simulations show this stratocumulus cloud to maintain a closed cellular structure, similar to observations. The updraft and downdraft cores self-organize into a larger meso-γ-scale convective pattern with the 1.5-TKE scheme, but the cores remain more isotropic with the CLUBB scheme. Additionally, the cores are often composed of liquid and ice instead of exclusively containing one or the other. Furthermore, these results provide insight into traditionally unresolved and unmeasurable aspects of an Arctic mixed-phase cloud. From analysis, this cloud's updraft and downdraft cores appear smaller than other closed-cell stratocumulus such as midlatitude stratocumulus and Arctic autumnal mixed-phase stratocumulus due to the weaker downdrafts and lower precipitation rates.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rauth, A.M.; Mohindra, J.K.
1981-12-01
The chemotherapeutic agent 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is used in the treatment of malignant melanoma where response rates of 15 to 30% have been reported. Some current interest exists in combining DTIC chemotherapy with localized high-dose (800 rads)-per-fraction radiotherapy in the treatment of unresectable metastatic melanoma. The present work investigates the radiosensitizing and chemotherapeutic properties of DTIC in an in vitro system using Chinese hamster ovary or HeLa cells and in vivo, using the KHT transplantable murine tumor. No evidence of a radiosensitizing effect of DTIC was found towards hypoxic or aerobic cells either in vitro or in vivo. In vitro, highmore » drug concentrations (1 mg/ml) were approximately 5 times more effective in killing hypoxic Chinese hamster ovary or HeLa cells than in killing aerobic cells over exposure times of 0 to 12 hr. The degree of toxicity was drug dose and temperature dependent but was not highly dependent on cell number or cell type. In vivo plasma levels of DTIC were measured with high-pressure liquid chromatography after i.p. injection of drug into C3H mice. At the highest drug doses tested, near the 50% lethal dose in mice for DTIC (0.5 mg/g), the drug was toxic to both aerobic and hypoxic tumor cells with some evidence of increased toxicity towards hypoxic cells. The present work suggests that DTIC may be more efficiently activated under hypoxic conditions as compared to aerobic conditions. The increased toxicity of DTIC under hypoxic versus aerobic conditions may prove to be a feature of this drug that can be exploited in its clinical use and in the design of new analogs of DTIC.« less
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Ionization in liquids. Progress report, September 1, 1977-April 30, 1981
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bakale, G.
1980-12-19
Quasifree electrons simulate the behavior of unsolvated or dry electrons in aqueous media including the special case of biological systems. A model of direct radiosensitization was developed based on dry charge-carriers having an extended lifetime in the sheath of structured water that surrounds polar biomolecules. In this model, the pre-solvation lifetimes of dry electrons increased with an increase in the rotational times of solvent molecules. During the development of this model, an increasing number of radiosensitizers were found to be carcinogenic. Measurement of the k/sub e/'s of known carcinogens and noncarcinogens revealed that carcinogens attached quasifree electrons at diffusion-controlled rates,more » whereas the k/sub e/'s of noncarcinogens were significantly less. To explore the k/sub e/-carcinogenicity correlation further, a study of quasifree electron attachment to the water pools of reversed micelles was conducted. The degree of structuredness of the water pools which determines the k/sub e/ of the reversed micellar systems was also controlled. Another approach to controlling the microenvironment of quasifree electrons in biological systems was done in studies of radiation-induced damage to DNA in concentrated DNA solutions. The high concentration of DNA introduces more structure into the solutions than that occurring in typical in vitro experiments. The structural enhancement by DNA extends the lifetime of unsolvated charge-carriers. The DNA-damaging effects of radiolyticaly produced charge-carriers were also determined in studies of synergistic mutagenesis in bacteria simultaneously exposed to ionizing radiation and electrophilic chemical carcinogens. The attachment-detachment equilibrium of nicotine in hexane solutions was also studied. Both the kinetics and the thermodynamics of electron reactions were studied. (ERB)« less
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Film stability in a vertical rotating tube with a core-gas flow.
NASA Technical Reports Server (NTRS)
Sarma, G. S. R.; Lu, P. C.; Ostrach, S.
1971-01-01
The linear hydrodynamic stability of a thin-liquid layer flowing along the inside wall of a vertical tube rotating about its axis in the presence of a core-gas flow is examined. The stability problem is formulated under the conditions that the liquid film is thin, the density and viscosity ratios of gas to liquid are small and the relative (axial) pressure gradient in the gas is of the same order as gravity. The resulting eigenvalue problem is first solved by a perturbation method appropriate to axisymmetric long-wave disturbances. The damped nature (to within the thin-film and other approximations made) of the nonaxisymmetric and short-wave disturbances is noted. In view of the limitations on a truncated perturbation solution when the disturbance wavenumber is not small, an initial value method using digital computer is presented. Stability characteristics of neutral, growing, and damped modes are presented showing the influences of rotation, surface tension, and the core-gas flow. Energy balance in a neutral mode is also illustrated.
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Infiltration characteristics of non-aqueous phase liquids in undisturbed loessal soil cores.
Wang, Yunqiang; Shao, Ming'an
2009-01-01
The widespread contamination of soils and aquifers by non-aqueous phase liquids (NAPL), such as crude oil, poses serious environmental and health hazards globally. Understanding the infiltration characteristics of NAPL in soil is crucial in mitigating or remediating soil contamination. The infiltration characteristics of crude and diesel oils into undisturbed loessal soil cores, collected in polymethyl methacrylate cylindrical columns, were investigated under a constant fluid head (3 cm) of either crude oil or diesel oil. The infiltration rate of both crude and diesel oils decreased exponentially as wetting depth increased with time. Soil core size and bulk density both had significant effects on NAPL infiltration through the undisturbed soil cores; a smaller core size or a greater bulk density could reduce oil penetration to depth. Compacting soil in areas susceptible to oil spills may be an effective stratage to reduce contamination. The infiltration of NAPL into soil cores was spatially anisotropic and heterogeneous, thus recording the data at four points on the soil core is a good stratage to improve the accuracy of experimental results. Our results revealed that crude and diesel oils, rather than their components, have a practical value for remediation of contaminated loessal soils.
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View planetary differentiation process through high-resolution 3D imaging
NASA Astrophysics Data System (ADS)
Fei, Y.
2011-12-01
Core-mantle separation is one of the most important processes in planetary evolution, defining the structure and chemical distribution in the planets. Iron-dominated core materials could migrate through silicate mantle to the core by efficient liquid-liquid separation and/or by percolation of liquid metal through solid silicate matrix. We can experimentally simulate these processes to examine the efficiency and time of core formation and its geochemical signatures. The quantitative measure of the efficiency of percolation is usually the dihedral angle, related to the interfacial energies of the liquid and solid phases. To determine the true dihedral angle at high pressure and temperatures, it is necessary to measure the relative frequency distributions of apparent dihedral angles between the quenched liquid metal and silicate grains for each experiment. Here I present a new imaging technique to visualize the distribution of liquid metal in silicate matrix in 3D by combination of focus ion beam (FIB) milling and high-resolution SEM image. The 3D volume rendering provides precise determination of the dihedral angle and quantitative measure of volume fraction and connectivity. I have conducted a series of experiments using mixtures of San Carlos olivine and Fe-S (10wt%S) metal with different metal-silicate ratios, up to 25 GPa and at temperatures above 1800C. High-quality 3D volume renderings were reconstructed from FIB serial sectioning and imaging with 10-nm slice thickness and 14-nm image resolution for each quenched sample. The unprecedented spatial resolution at nano scale allows detailed examination of textural features and precise determination of the dihedral angle as a function of pressure, temperature and composition. The 3D reconstruction also allows direct assessment of connectivity in multi-phase matrix, providing a new way to investigate the efficiency of metal percolation in a real silicate mantle.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Meijne, E.I.; van der Winden-van Groenewegen, R.J.; Ploemacher, R.E.
The sensitivity for x-irradiation of a series of hematopoietic stem cell populations has been determined. The most primitive cells identified, cells with marrow-repopulating ability (MRA), showed the highest degree of radioresistance. These MRA cells which generate many secondary day-twelve spleen colony-forming units (MRA(CFU-S-12)) or colony-forming units in culture (MRA(CFU-C)) in the marrow of primary recipients had Do values equal to 1.18 and 1.13 Gy, respectively. The more mature CFU-S-12 had intermediate radiosensitivity (Do = 0.94 Gy), whereas the less primitive CFU-S-7 were the most radiosensitive (Do = 0.71 Gy). The in vitro colony-forming precursor cells (CFU-C) showed low radiosensitivity. Thesemore » data clearly show that the most primitive hematopoietic stem cell measured is less sensitive to ionizing radiation than generally has been assumed on the basis of measurements on CFU-S-7 or CFU-S-12.« less
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Do no harm--normal tissue effects
NASA Technical Reports Server (NTRS)
Hall, E. J.
2001-01-01
Radiation therapy confers enormous benefits that must be balanced against the possibilities for harm including late toxicity in normal tissues and radiation-induced second malignancies. A small percentage of patients experience severe late complications. The question is, do these late sequelae occur randomly, or are they confined to individuals who are genetically predisposed to radiosensitivity. Experiments with knockout mice and with patients demonstrate that individuals heterozygous for a number of genes appear to be radiosensitive. If radiosensitive patients were identified prospectively by genetic analysis, they could be spared the trauma of late sequelae. Several large studies have shown a statistically significant excess of radiation-induced malignancies in radiotherapy patients. Most second cancers are carcinomas, developing in the lining cells of the body often remote from the treatment site. Radiation-induced sarcomas appear only in the heavily irradiated areas. These are small in number but appear with a very high relative risk.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kushnuruk, V.A.
1962-01-01
ABS>Earlier reports suggest that the radiosensitivity of birds varies according to the systematic position of the species in question. To study this question in greater detail, birds belonging to different species were exposed to x rays and the LD/sub 50/ for 30 days recorded. During exposure, the birds were kept in a small cage but could move freely. Five different species were investigated: the greenfinch (Chloris chloris L.), goldfinch (Carduelis carduelis L.), linnet (Acantis cannabina L.), house sparrow (Passer domesticus), and the canary (Serinus canarina L.). It appeared that the radiosensitivity of the birds moved within a fairly narrow rangemore » quite independently of the species. The LD/ sub 50/ for 30 days varied in the 5 species in question between 400 and 625 r. All birds showed disorders of the coordination of movements, in the reflex governing the picking of food, in flight, and in perching. (OTS)« less
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Variation in tumor response to fluosol-DA (20%)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sasai, K.; Ono, K.; Nishidai, T.
1989-05-01
The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO/sub 2/) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C/sub 3/H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors,more » only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Miles, Edward F.; Tatsukawa, Yoshimi; Funamoto, Sachiyo
Purpose . There is evidence in the literature of increased maternal radiosensitivity during pregnancy. Materials and Methods . We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions . Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximatelymore » 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased radiosensitivity in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased radiosensitivity.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Mashiba, Harukazu; Matsunaga, Keiko; Hata, Kazuo
1991-01-01
The radiosensitizing effect of the nitroimidazole derivative RK28 and diethyldithiocarbamate (DDC), which is an inhibitor of superoxide dismutase activity, was examined in vitro by using Meth A tumor cells. The radiosensitizing effect of 0.5 mM RK28 was observed in both of 10 Gy and 15 Gy irradiated groups. The addition of 5 {times} 10{sup {minus}7} M DDC also enhanced the radiation-induced proliferation inhibition. Marked enhancement of the anti-proliferative effect was observed in combined use of 0.2 mM or 0.5 mM RK28 with 2 {times} 10 M or 5 {times} 10{sup {minus}7} M DDC. These results suggest that enhanced oxygen effectmore » could be expected through combined use of the ionizing irradiation with both of these agents.« less
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Rockets, radiosensitizers, and RRx-001: an origin story part I.
Oronsky, Bryan; Scicinski, Jan; Ning, Shoucheng; Peehl, Donna; Oronsky, Arnold; Cabrales, Pedro; Bednarski, Mark; Knox, Susan
2016-03-01
From Adam and Eve, to Darwinism, origin stories attempt to fill in the blanks, connect the dots, and define the turning points that are fundamental to subsequent developments. The purpose of this review is to present the origin story of a one-of-a-kind anticancer agent, RRx-001, which emerged from the aerospace industry as a putative radiosensitizer; not since the dynamite-to-dilator transformation of nitroglycerin in 1878 or the post-World War II explosive-to-elixir conversion of hydralazine, an ingredient in rocket fuel, to an antihypertensive, an antidepressant and an antituberculant, has energetic chemistry been harnessed for therapeutic purposes. This is Part 1 of the radiosensitization story; Parts 2 and 3, which detail the crossover activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wolters, H.; Kelholt, D.; Konings, A.W.
1987-02-01
The interaction of heat and X irradiation was studied in normal and polyunsaturated fatty acid (PUFA) substituted mouse fibroblast LM cells. As a result of the substitution the membranes of the PUFA cells were more fluid than the membranes of the normal cells. Three different heat doses were applied (60 min 42 degrees C, 20 min 43 degrees C, and 10 min 44 degrees C) in combination with single or split doses of X rays. Heat radiosensitization was the largest for the 60 min 42 degrees C treatment. Heat radiosensitization and the heat-induced inhibition of the rate of sublethal damagemore » repair were the same for the normal and the PUFA cells. It is concluded from the experiments reported that the processes of hyperthermic inhibition of SLD repair and hyperthermic radiosensitization are independent of membrane fluidity and membrane fatty acid composition.« less
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Mechanism of radiosensitization by porphyrins.
Luksiene, Zivile; Labeikyte, Danute; Juodka, Benediktas; Moan, Johan
2006-01-01
According to our previous data, hematoporphyrin dimethyl ether (HPde) at concentrations useful for photodynamic therapy can radiosensitize aggressive Ehrlich ascite carcinoma (EAT) to 2Gy irradiation inducing total tumour growth inhibition. The aim of this study was to further investigate the possible mechanism of radiosensitization of EAT by dicarboxylic porphyrin-HPde. Our results reveal that HPde is inducing several rearrangements in the EAT cells: 1.2 x 10-6 M of the photosensitizer diminishes the number of cells in mitosis by a factor of 3, increases the number of cells in the S phase of the cell cycle, modifies the activities of antioxidant enzymes glutation S-transferase (GST) and DT-diaphorase (DTD), and eventually induces slight apoptosis. Moreover, it was shown that HPde is a ligand of peripheral benzodiazepine receptor (PBR). Named "house keeper," PBR is usually responsible for all these perturbations, which, in our case, act in concert with the following ionizing radiation, producing the interaction of two antiproliferative/destructive factors.
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Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.
He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo
2014-02-01
Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.
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NASA Technical Reports Server (NTRS)
Druzhinin, Y. P.; Romanov, Y. A.; Vatsek, A.
1974-01-01
Radiosensitivity of individual phases of the mitotic cycle was studied in synchronous cell cultures and in several biological objects. It was found that radiosensitivity changed essentially according to phases of the mitotic cycle, depending on the kind of cells, evaluation criteria and the radiation dosage. Tests on partially synchronized HeLa cell populations, according to the criterion of survival, showed them most sensitive during mitosis, as well as in later G sub 1- or early DNA-synthesizing stages. With radiation in doses of 300 rad, the proportion of surviving cells showed a sensitivity directly before DNA synthesis of approximately 4 times higher than the later S-phase and during the major portion of G sub 1- and G sub 2-periods. Sensitivity of cells in mitosis was approximately 3 times higher than in late G sub 1- and early S-phases.
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NASA Astrophysics Data System (ADS)
Tsuno, K.; Dasgupta, R.; Grewal, D. S.
2017-12-01
Constraining the carbon (C) fractionation between the silicate magma ocean (MO) and core-forming alloy liquid is required to determine the origin and evolution of C between reservoirs such as atmosphere, crust, mantle, and core of terrestrial planets. [1]. Alloy-silicate partitioning experiments of C have shown that preferential fractionation of C into the alloy liquid would have left the bulk silicate Earth (BSE) devoid of C [2-4]. Merger of a sulfur (S)-rich differentiated planetary embryo into the proto-Earth could have supplied almost the entire C budget of the present-day BSE [5], however, experimental data on the systematic effect of S on C solubility in Fe-Ni alloy liquid and its partitioning between the alloy liquid and silicate melt are lacking. We have performed multi anvil experiments with alloy-silicate±glassy carbon mixtures at 6-13 GPa and 1800-2000 °C, fO2 of ΔIW of -0.4 to -2.3, using graphite or MgO capsules and varying alloy S content from 10 to 36 wt.%. We find that C content of the alloy liquid decreases from 4.6 to 0.2 wt.% with increasing alloy S content of 10 to 36 wt.%. Temperature has a small positive effect and pressure has little effect on alloy C solubility. Alloy-silicate partition coefficient of C also decreases with increasing alloy S content at a given P-T-fO2. We used the data to quantify the distribution of C between the silicate MO and core-forming alloy liquid of an S-rich planetary embryo. The model calculations using our data suggest that the addition of a relatively oxidized, C-poor ( 0.3 wt.%) and S-rich ( 3 wt.%) large embryo (6-20% of the present-day Earth mass) to a volatile-poor growing Earth can establish the C and S contents [6, 7] and C/S ratio [8] in BSE. The resulting core composition after the accretion and core formation process is estimated to be C- and S-poor ( 0.05 wt.% and 0.6 wt.%, respectively). On the other hand, a single stage core formation on Mars that results in a core with 8-10 wt.% S can yield a mantle with terrestrial-mantle like carbon abundance if the bulk Mars contains 0.6 wt.% C and 1.5-1.7 wt.% S. [1] Dasgupta (2013) RiMG. [2] Dasgupta et al. (2013) GCA. [3] Chi et al. (2014) GCA. [4] Li et al. (2015) EPSL. [5] Li et al. (2016) Nat. Geo. [6] Dasgupta & Hirschmann (2010) EPSL. [7] Palme & O'Neill (2013), Treat. Geochem. [8] Hirschmann (2016) Am Min.
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X-ray Radiography Measurements of Shear Coaxial Rocket Injectors
2013-05-07
injector EPL profiles have elliptical shape expected from a solid liquid jet EPL decreases as liquid core is atomized and droplets are...study diesel, swirl, gas-centered swirl-coaxial, impingers, and aerated liquid jet injectors Use a monochromatic beam of x-rays at a synchrotron...Shear coaxial jets can be found in a number of combustion devices – Turbofan engine exhaust, air blast furnaces, and liquid rocket engines
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Solid0Core Heat-Pipe Nuclear Batterly Type Reactor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ehud Greenspan
This project was devoted to a preliminary assessment of the feasibility of designing an Encapsulated Nuclear Heat Source (ENHS) reactor to have a solid core from which heat is removed by liquid-metal heat pipes (HP).
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On-Chip generation of polymer microcapsules through droplet coalescence
NASA Astrophysics Data System (ADS)
Eqbal, Md Danish; Gundabala, Venkat; Gundabala lab Team
Alginate microbeads and microcapsules have numerous applications in drug delivery, tissue engineering and other biomedical areas due to their unique properties. Microcapsules with liquid core are of particular interest in the area of cell encapsulation. Various methods such as coacervation, emulsification, micro-nozzle, etc. exist for the generation of microbeads and microcapsules. However, these methods have several drawbacks like coagulation, non-uniformity, and polydispersity. In this work we present a method for complete on chip generation of alginate microcapsules (single core as well as double core) through the use of droplet merging technique. For this purpose, a combined Coflow and T-junction configuration is implemented in a hybrid glass-PDMS (Polydimethylsiloxane) microfluidic device. Efficient generation is achieved through precise matching of the generation rates of the coalescing drops. Through this approach, microcapsules with intact single and double (liquid) cores surrounded by alginate shell have been successfully generated and characterized.
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The lead isotopic age of the Earth can be explained by core formation alone.
Wood, Bernard J; Halliday, Alex N
2010-06-10
The meaning of the age of the Earth defined by lead isotopes has long been unclear. Recently it has been proposed that the age of the Earth deduced from lead isotopes reflects volatile loss to space at the time of the Moon-forming giant impact rather than partitioning into metallic liquids during protracted core formation. Here we show that lead partitioning into liquid iron depends strongly on carbon content and that, given a content of approximately 0.2% carbon, experimental and isotopic data both provide evidence of strong partitioning of lead into the core throughout the Earth's accretion. Earlier conclusions that lead is weakly partitioned into iron arose from the use of carbon-saturated (about 5% C) iron alloys. The lead isotopic age of the Earth is therefore consistent with partitioning into the core and with no significant late losses of moderately volatile elements to space during the giant impact.
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Transformable liquid-metal nanomedicine
NASA Astrophysics Data System (ADS)
Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen
2015-12-01
To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.
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Peng, Pei; Wang, Wei; Zhang, Li; Su, Shiguang; Wang, Jiahui
2013-12-04
The absorbance characteristics and influential factors on these characteristics for a liquid-phase gas sensor, which is based on gas-permeable liquid core waveguides (LCWs), are studied from theoretical and experimental viewpoints in this paper. According to theory, it is predicted that absorbance is proportional to the analyte concentration, sampling time, analyte diffusion coefficient, and geometric factor of this device when the depletion layer of the analyte is ignored. The experimental results are in agreement with the theoretical hypothesis. According to the experimental results, absorbance is time-dependent and increasing linearly over time after the requisite response time with a linear correlation coefficient r(2)>0.999. In the linear region, the rate of absorbance change (RAC) indicates improved linearity with sample concentration and a relative higher sensitivity than instantaneous absorbance does. By using a core liquid that is more affinitive to the analyte, reducing wall thickness and the inner diameter of the tubing, or increasing sample flow rate limitedly, the response time can be decreased and the sensitivity can be increased. However, increasing the LCW length can only enhance sensitivity and has no effect on response time. For liquid phase detection, there is a maximum flow rate, and the absorbance will decrease beyond the stated limit. Under experimental conditions, hexane as the LCW core solvent, a tubing wall thickness of 0.1 mm, a length of 10 cm, and a flow rate of 12 mL min(-1), the detection results for the aqueous benzene sample demonstrate a response time of 4 min. Additionally, the standard curve for the RAC versus concentration is RAC=0.0267c+0.0351 (AU min(-1)), with r(2)=0.9922 within concentrations of 0.5-3.0 mg L(-1). The relative error for 0.5 mg L(-1) benzene (n=6) is 7.4±3.7%, and the LOD is 0.04 mg L(-1). This research can provide theoretical and practical guides for liquid-phase gas sensor design and development based on a gas-permeable Teflon AF 2400 LCW. Copyright © 2013 Elsevier B.V. All rights reserved.
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Possibility study of gasifier with axial circulating flue gas for reducing Tar
NASA Astrophysics Data System (ADS)
Poowadin, T.; Polsongkram, M.; Khantikomol, P.
2018-01-01
This present research article aims to study the possibility of gasification by axial core flue gas circulating kiln and find the efficiency of syngas production. An axial core flue gas circulating tube was installed in the center of the updraft gasifier in purposing of tar reducing. In the present study, the eucalyptus wood chip 4, 8, and 10 kg with the moisture content 16% were examined. Several type-K thermocouples were employed to measure the temperatures at preheat, combustion, reduction, pyrolysis, drying, and gas outlet zone. The results showed that the temperatures in the combustion and the reduction zone of the kiln with the axial core flue gas recirculating were lower than the kiln without the core owing to installing the core would reduce the combustion zone area in biomass burning. Obviously, the temperature in the pyrolysis and drying zone were nearly the same as both with and without the core. In consideration of syngas components, it was found that CO production from the gasifier with the core was higher than the gasifier without the core about 25%. Other gases, however, were almost same. The syngas production efficiency obtained from the gasifier with the core decreased with increasing the mass of biomass. It showed that the highest efficiency was 30% at 4 kg supplying biomass. In comparison, the efficiencies of both the kilns with and without the core were not different. For liquid product, the amount of liquid decreased about 47.23% comparing with the gasifier without the core.
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Chen, Xu; Wu, Lei; Li, Dezhi; Xu, Yanmei; Zhang, Luping; Niu, Kai; Kong, Rui; Gu, Jiaoyang; Xu, Zihan; Chen, Zhengtang; Sun, Jianguo
2018-06-02
Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR-18a-5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR-18a-5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR-18a-5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF-1α) as the targets of miR-18a-5p. The mRNA and protein expressions of ATM and HIF-1α were dramatically downregulated by miR-18a-5p in vitro and in vivo. Clinically, plasma miR-18a-5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR-18a-5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR-18a-5p-high group than in miR-18a-5p-low group (P < .001). A tendency demonstrated that the median local progression-free survival (PFS) from radiotherapy was longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .281). The sensitivity and specificity of plasma miR-18a-5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR-18a-5p increases the radiosensitivity in lung cancer cells and CD133 + stem-like cells via downregulating ATM and HIF-1α expressions. Plasma miR-18a-5p would be an available indicator of radiosensitivity in lung cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe
2011-09-01
Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR=53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR=38.26; 95% CI, 1.19-1232.52). To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic polymorphisms may be promising candidates for predicting acute radiosensitivity, but further studies are necessary to confirm our findings. Copyright © 2011 Elsevier Inc. All rights reserved.
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Initial Testing of the Stainless Steel NaK-Cooled Circuit (SNaKC)
NASA Technical Reports Server (NTRS)
Garber, Anne; Godfroy, Thomas
2007-01-01
An actively pumped alkali metal flow circuit, designed and fabricated at the NASA Marshall Space Flight Center, is currently undergoing testing in the Early Flight Fission Test Facility (EFF-TF). Sodium potassium (NaK) was selected as the primary coolant. Basic circuit components include: simulated reactor core, NaK to gas heat exchanger, electromagnetic liquid metal pump, liquid metal flowmeter, load/drain reservoir, expansion reservoir, test section, and instrumentation. Operation of the circuit is based around the 37-pin partial-array core (pin and flow path dimensions are the same as those in a full core), designed to operate at 33 kWt. This presentation addresses the construction, fill and initial testing of the Stainless Steel NaK-Cooled Circuit (SNaKC).
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Fracture-induced flow and liquid metal transport during core formation
NASA Astrophysics Data System (ADS)
Jones, V.; Petford, N.; Rushmer, T.; Wertheim, D.
2008-12-01
The most important event in the early history of the earth was the separation of its iron-rich core. Core formation induced profound chemical fractionations and extracted into the core most of Earth's iron and siderophile elements (Ni, Co, Au, Pt, W, Re), leaving the silicate crust and mantle with strong depletions of these elements relative to primitive planetary material. Recent measurements of radiogenic 182W anomalies in the silicate Earth, Mars and differentiated meteorites imply that planetesimals segregated metallic cores within a few Myr of the origin of the solar system. Various models have been put forward to explain the physical nature of the segregation mechanism (Fe-diapirs, 'raining' through a magma ocean), and more recently melt flow via fractures. In this contribution we present the initial results of a numerical study into Fe segregation in a deforming silicate matrix that captures the temperature-dependent effect of liquid metal viscosity on the transport rate. Flow is driven by pressure gradients associated with impact deformation in a growing planetesimal and the fracture geometry is constrained by experimental data on naturally deformed H6 chondrite. Early results suggest that under dynamic conditions, fracture-driven melt flow can in principle be extremely rapid, leading to a significant draining of the Fe-liquid metal and siderophile trace element component on a timescale of hours to days. Fluid transport in planetesimals where deformation is the driving force provides an attractive and simple way of segregating Fe from host silicate as both precursor and primary agent of core formation
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2006-07-01
ATM genetic variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for each mutation examined. 15. SUBJECT...women without breast cancer. An additional objective is to determine the functional impact upon the protein encoded by the ATM gene for each mutation ...each ATM variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for mutations identified. Body STATEMENT
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lai, Xiaojing; Chen, Bin; Wang, Jianwei
During the formation of the Earth's core, the segregation of metallic liquids from silicate mantle should have left behind evident geochemical imprints on both the mantle and the core. Some distinctive geochemical signatures of the mantle-derived rocks likely own their origin to the metal-silicate differentiation of the primitive Earth, setting our planet apart from undifferentiated meteorites as well as terrestrial planets or moons isotopically and compositionally. Understanding the chemical evolution of terrestrial planetary bodies requires knowledge on properties of both liquid iron alloys and silicates equilibrating under physicochemical conditions pertinent to the deep magma ocean. Here we report experimental andmore » computational results on the pressure-induced structural evolution of iron-nickel liquids alloyed with carbon. Our X-ray diffraction experiments up to 7.3 gigapascals (GPa) demonstrate that Fe-Ni (Fe90Ni10) liquids alloyed with 3 and 5 wt % carbon undergo a polyamorphic liquid structure transition at approximately 5 GPa. Corroborating the experimental observations, our first-principles molecular dynamic calculations reveal that the structural transitions result from the marked prevalence of three-atom face-sharing polyhedral connections in the liquids at >5 GPa. The structure and polyamorphic transitions of liquid iron-nickel-carbon alloys govern their physical and chemical properties and may thus cast fresh light on the chemical evolution of terrestrial planets and moons.« less
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Radiosensitization of HT-29 cells and xenografts by the nitric oxide donor DETANONOate.
Gao, Xiaohuan; Saha, Debabrata; Kapur, Payal; Anthony, Thomas; Livingston, Edward H; Huerta, Sergio
2009-08-01
Mechanisms of radioresistance in rectal cancer remain unclear. To determine mechanisms of radioresistance in rectal cancer cells and to assess the role of the nitric oxide donor DETANONOate as a radiosensitizing agent. Survival was determined by clonogenic assays, apoptosis by PARP-1 cleavage, and phenotypic differences by Western blot analysis. SCID mice bearing HT-29 xenografts were treated with ionizing radiation (IR) [2.0 Gy x 5], DETANONOate [0.4 mg/kg i.p.], or combination treatment. Colorectal cancer HT-29-p53-null cells were resistant and HCT-116-p53 wild-type cells sensitive to IR, which correlated with cleaved PARP-1. Increased levels of p21 occurred in HCT-116 cells, while Bcl-2 and survivin were elevated in HT-29 cells. Radiosensitization was achieved with a substantial elevation of cleaved PARP-1 in DETANONOate-HT-29-treated versus control cells, which was accompanied by elevation of p21, p27, and BAX, and a concomitant decrease in Bcl-2. SCID mice bearing HT-29 xenografts demonstrated a 37.6%, 51.1%, and 70.1% inhibition in tumor growth in mice receiving IR, DETANONOate, and combination treatment versus control, respectively. Radioresistant HT-29 cells are p53-null and have substantially decreased levels of p21. DETANONOate radiosensitized HT-29 cells in vitro and in vivo by an additive effect in apoptosis.
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Ihara, Makoto; Takeshita, Satoshi; Okaichi, Kumio; Okumura, Yutaka; Ohnishi, Takeo
2014-03-01
From the role of double strand DNA dependent protein kinase (DNA-PKcs) activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks (DSBs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in X-ray irradiated cells. DNA-PKcs deficient mouse, Chinese hamster and human cultured cells were compared to the parental wild-type cells. The radiosensitivities, the number of DSBs and DNA-PKcs activities after heat-treatment were measured. Both DNA-PKcs deficient cells and the wild-type cells showed increased radiosensitivities after heat-treatment. The wild-type cells have two repair processes; fast repair and slow repair. In contrast, DNA-PKcs deficient cells have only the slow repair process. The fast repair component apparently disappeared by heat-treatment in the wild-type cells. In both cell types, additional heat exposure enhanced radiosensitivities. Although DNA-PKcs activity was depressed by heat, the inactivated DNA-PKcs activity recovered during an incubation at 37 °C. DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity. It was suggested that NHEJ is the major process used to repair X-ray-induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair provides additional secondary levels of DSB repair. The thermo-sensitisation in X-ray-irradiated cells depends on the inhibition of NHEJ repair through the depression of DNA-PKcs activities.
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Merle, Patrick; Gueugneau, Marine; Teulade-Fichou, Marie-Paule; Müller-Barthélémy, Mélanie; Amiard, Simon; Chautard, Emmanuel; Guetta, Corinne; Dedieu, Véronique; Communal, Yves; Mergny, Jean-Louis; Gallego, Maria; White, Charles; Verrelle, Pierre; Tchirkov, Andreï
2015-11-06
Telomeres are nucleoprotein structures at the end of chromosomes which stabilize and protect them from nucleotidic degradation and end-to-end fusions. The G-rich telomeric single-stranded DNA overhang can adopt a four-stranded G-quadruplex DNA structure (G4). Stabilization of the G4 structure by binding of small molecule ligands enhances radiosensitivity of tumor cells, and this combined treatment represents a novel anticancer approach. We studied the effect of the platinum-derived G4-ligand, Pt-ctpy, in association with radiation on human glioblastoma (SF763 and SF767) and non-small cell lung cancer (A549 and H1299) cells in vitro and in vivo. Treatments with submicromolar concentrations of Pt-ctpy inhibited tumor proliferation in vitro with cell cycle alterations and induction of apoptosis. Non-toxic concentrations of the ligand were then combined with ionizing radiation. Pt-ctpy radiosensitized all cell lines with dose-enhancement factors between 1.32 and 1.77. The combined treatment led to increased DNA breaks. Furthermore, a significant radiosensitizing effect of Pt-ctpy in mice xenografted with glioblastoma SF763 cells was shown by delayed tumor growth and improved survival. Pt-ctpy can act in synergy with radiation for efficient killing of cancer cells at concentrations at which it has no obvious toxicity per se, opening perspectives for future therapeutic applications.
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Uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer.
Ito, Emma; Yue, Shijun; Moriyama, Eduardo H; Hui, Angela B; Kim, Inki; Shi, Wei; Alajez, Nehad M; Bhogal, Nirmal; Li, Guohua; Datti, Alessandro; Schimmer, Aaron D; Wilson, Brian C; Liu, Peter P; Durocher, Daniel; Neel, Benjamin G; O'Sullivan, Brian; Cummings, Bernard; Bristow, Rob; Wrana, Jeff; Liu, Fei-Fei
2011-01-26
Head and neck cancer (HNC) is the eighth most common malignancy worldwide, comprising a diverse group of cancers affecting the head and neck region. Despite advances in therapeutic options over the last few decades, treatment toxicities and overall clinical outcomes have remained disappointing, thereby underscoring a need to develop novel therapeutic approaches in HNC treatment. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, was identified from an RNA interference-based high-throughput screen as a tumor-selective radiosensitizing target for HNC. UROD knockdown plus radiation induced caspase-mediated apoptosis and cell cycle arrest in HNC cells in vitro and suppressed the in vivo tumor-forming capacity of HNC cells, as well as delayed the growth of established tumor xenografts in mice. This radiosensitization appeared to be mediated by alterations in iron homeostasis and increased production of reactive oxygen species, resulting in enhanced tumor oxidative stress. Moreover, UROD was significantly overexpressed in HNC patient biopsies. Lower preradiation UROD mRNA expression correlated with improved disease-free survival, suggesting that UROD could potentially be used to predict radiation response. UROD down-regulation also radiosensitized several different models of human cancer, as well as sensitized tumors to chemotherapeutic agents, including 5-fluorouracil, cisplatin, and paclitaxel. Thus, our study has revealed UROD as a potent tumor-selective sensitizer for both radiation and chemotherapy, with potential relevance to many human malignancies.
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Theranostic gold-magnetite hybrid nanoparticles for MRI-guided radiosensitization.
Maniglio, D; Benetti, F; Minati, L; Jovicich, J; Valentini, A; Speranza, G; Migliaresi, C
2018-08-03
The main limitation of drug-enhanced radiotherapy concerns the difficulty to evaluate the effectiveness of cancer targeting after drug administration hindering the standardization of therapies based on current radiosensitizing compounds. The challenge regards the development of systems able to combine imaging and radiotherapy enhancement in order to perform highly reliable cancer theragnosis. For these reasons, gold-magnetite hybrid nanoparticles (H-NPs) are proposed as innovative theranostic nanotools for imaging-guided radiosensitization in cancer treatment. In this work we propose a novel method for the synthesis of hydrophilic and superparamagnetic Tween20-stabilized gold-magnetite H-NPs. Morphology and chemical composition of nanoparticles were assessed by transmission electron microscopy, x-ray diffraction analysis and ion-coupled plasma optical emission spectroscopy. Colloidal stability and magnetic properties of nanoparticles were determined by dynamic light scattering and magnetometry. The potentialities of H-NPs for magnetic resonance imaging were studied using a human 4T-MRI scanner. Nanoparticles were proven to induce concentration-dependent contrast enhancement in T2*-weighted MR-images. The cytotoxicity, the cellular uptake and the radiosensitization activity of H-NPs were investigated in human osteosarcoma MG63 cell cultures and murine 3T3 fibroblasts, using specific bioassays and laser scanning confocal microscopy. H-NPs did not exhibit significant toxicity and were demonstrated to be internalized by cells. A significant x-ray enhancement at specific H-NPs exposure concentrations was evidenced on MG63 cell line.
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Radiation-induced radioresistance of mammals and risk assessment
NASA Astrophysics Data System (ADS)
Smirnova, O.; Yonezawa, M.
It is shown experimentally that a preliminary low dose exposure can induce radioresistance in mice in two (early and late) periods after preirradiation. The manifestation of such effects is reduced mortality of pre-exposed specimens after challenge acute irradiation, the reason of the animal death being the hematopoietic subsyndrome of the acute radiation syndrome. Therefore, proceeding from the radiobiological concept of the critical system, the theoretical investigation of the influence of preirradiation on mammalian radiosensitivity is conducted by making use of mathematical models of the vital body system, hematopoiesis. Modeling results make it possible to elucidate the mechanisms of the radioprotection effect of low level priming irradiation on mammals. Specifically, the state of acquired radioresistance in mice is caused by reduced radiosensitivity of lymphopoietic and thrombocytopoietic systems in the early period and by reduced radiosensitivity of granulocytopoietic system in the late period after preirradiation. It is important to emphasize that the evaluations of the duration of the early and late periods of postirradiation radioresistance in mice, carried out on the basis of the modeling and experimental investigations, practically coincide. All this demonstrates the effectiveness of joint modeling and experimental methods in studies and predictions of modification effects of preirradiation on mammalian radiosensitivity. The results obtained show the importance of accounting such effects in radiation risk assessments for cosmonauts and astronauts on long-term missions.
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Su, L N; Little, J B
1992-08-01
Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. Cells transfected with EJ ras alone showed no morphological alterations nor significant changes in radiosensitivity. Cell clones expressing ras and/or SV40 T-antigen showed a reduced requirement for serum supplements, an increase in aneuploidy and chromosomal aberrations, and enhanced growth in soft agar as an early cellular response to SV40 T-antigen expression. The sequential order of transfection with SV40 T-antigen and ras influenced radio-sensitivity but not the induction of morphological changes. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself.
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Ziemann, Frank; Seltzsam, Steve; Dreffke, Kristin; Preising, Stefanie; Arenz, Andrea; Subtil, Florentine S B; Rieckmann, Thorsten; Engenhart-Cabillic, Rita; Dikomey, Ekkehard; Wittig, Andrea
2017-12-01
At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. Patients with HPV positive tumors possess a far better prognosis than those with HPV negative cancers. Therefore, new therapeutic strategies are needed to improve the outcome especially of the latter one as well as quality of life for all HNSCC patients. Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. Surprisingly, all HPV positive cell lines were found to be defective in HR. In contrast, HPV negative strains demonstrated efficient HR, which was completely suppressed by roscovitine. In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. Due to a defect in HR, all HPV positive cell lines were efficiently radiosensitized by the PARP-1 inhibitor olaparib. In contrast, in HPV negative cell lines a significant radiosensitization by olaparib was only achieved when combined with roscovitine.
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DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer
Ou, Yao; Zhang, Quan; Tang, Yiting; Lu, Zhonghua; Lu, Xujing; Zhou, Xifa; Liu, Changmin
2018-01-01
Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca-109 and TE-1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca-109 cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect changes to microvessels and tumor growth by immunohistochemistry (IHC). RNA-seq was used to identify differentially expressed genes. We found that RG108 increased the radiosensitivity of EC cells. Apoptosis and G2/M-phase arrest were induced by X-ray irradiation and were significantly enhanced by RG108. In addition, growth of tumor xenografts from the Eca-109 cells was significantly inhibited by irradiation in combination with RG108. The RNA-seq analysis revealed that, compared with radiation alone, X-ray irradiation in combination with RG108 altered the expression of 121 genes in multiple pathways, including the TGF-β signaling pathway and the Epstein-Barr virus infection pathway. In conclusion, RG108 induced radiosensitivity in EC cells both in vitro and in vivo. PMID:29328411
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The nitric oxide donor JS-K sensitizes U87 glioma cells to repetitive irradiation.
Heckler, Max; Osterberg, Nadja; Guenzle, Jessica; Thiede-Stan, Nina Kristin; Reichardt, Wilfried; Weidensteiner, Claudia; Saavedra, Joseph E; Weyerbrock, Astrid
2017-06-01
As a potent radiosensitizer nitric oxide (NO) may be a putative adjuvant in the treatment of malignant gliomas which are known for their radio- and chemoresistance. The NO donor prodrug JS-K (O2-(2.4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate) allows cell-type specific intracellular NO release via enzymatic activation by glutathione-S-transferases overexpressed in glioblastoma multiforme. The cytotoxic and radiosensitizing efficacy of JS-K was assessed in U87 glioma cells in vitro focusing on cell proliferation, induction of DNA damage, and cell death. In vivo efficacy of JS-K and repetitive irradiation were investigated in an orthotopic U87 xenograft model in mice. For the first time, we could show that JS-K acts as a potent cytotoxic and radiosensitizing agent in U87 cells in vitro. This dose- and time-dependent effect is due to an enhanced induction of DNA double-strand breaks leading to mitotic catastrophe as the dominant form of cell death. However, this potent cytotoxic and radiosensitizing effect could not be confirmed in an intracranial U87 xenograft model, possibly due to insufficient delivery into the brain. Although NO donor treatment was well tolerated, neither a retardation of tumor growth nor an extended survival could be observed after JS-K and/or radiotherapy.
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Individual Genetic Susceptibility
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eric J. Hall
2008-12-08
Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimentalmore » radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.« less
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Wang, Buhai; Ge, Yizhi; Gu, Xiang
2016-10-06
Assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of esophageal cancer cell line in vitro. Three esophageal cancer cell line cells were exposed to X-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell growth curve, and flow cytometry was performed to assess the cell apoptosis. The radiosensitizing effects of TNF-α were detected by cell colony formation assay. Western blotting was applied to observe the expression of NF-κB and caspase-3 protein in the exposed cells. Our results indicated that cellular inhibition rate increased over time, the strongest is combined group (P < 0.05). Western blotting showed that the decline expression of NF-κB protein was stated between only rhTNF-α and only X-ray radiation group and the maximum degree was manifested in combined group. Caspase-3 protein content expression just works opposite. Three kinds of cells in the NF-κB protein were similar without rhTNF-α. Then SEG1 NF-κB protein content was reduced more than other two kinds. We concluded that the cells treated with TNF-α showed significantly suppressed cell proliferation, increasing the cell apoptosis, and caspase-3 protein expression after X-ray exposure. TNF-α can enhance the radiosensitivity of esophageal cancer to enhancing the effect of the former.
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The thermal evolution and dynamo generation of Mercury with an Fe-Si core
NASA Astrophysics Data System (ADS)
Knibbe, Jurrien
2017-04-01
The present day partially liquid (as opposed to fully solidified) Fe-rich core of Mercury is traditionally explained by assuming a substantial amount of S to be present in the core (e.g. Grott et al., 2011), because S lowers the core's melting temperature. However, this assumption has problematic implications: Mercury's large Fe-rich core and measured low FeO surface content are indicative of an oxygen poor bulk composition, which is consistent with the volatile-poor material that is expected to have condensed from the solar nebula close to the Sun. In contrast, S is a moderately volatile element. Combined with the high S content of Mercury's crust and (likely) mantle, as indicated by the measured high S/Si surface fraction, the resulting high planetary S abundance is difficult to reconcile with a volatile poor origin of the planet. Additionally, the observed low magnetic field strength is most easily explained if compositional buoyancy fluxes are absent [Manglik et al., 2010], yet such fluxes are produced upon solidifying a pure Fe inner core from Fe-S liquid. Alternatively, both Mercury's high S/Si and Mg/Si surface ratios (Nittler et al., 2011) may indicate that a siderophile fractionation of Si and lithophile fractionation of S took place during Mercury's core-mantle differentiation. This fractionation behaviour of these elements is supported by metal/silicate partitioning experiments that have been performed at the low oxygen conditions inferred for Mercury [e.g. Chabot et al., 2014]. Mercury's bulk composition, in terms of S/Si and Fe/Si ratios, would also approach that of meteorites that are considered as potential building blocks of the planet if the core is Si-rich and S-poor. Here we simulate the thermal evolution of Mercury with an Fe-Si core. Results show that an Fe-Si core can remain largely molten until present, without the need for S. An Fe-Si core also has interesting implications for Mercury's core-convection regime and magnetic field generation. The non-preferential Si fractionation between solid and liquid metal does not produce a compositional gradient, such that compositional buoyancy fluxes are negligible. Additionally, thermally driven core convection is more efficient as a result of a high latent heat release upon solidifying Si-rich metal. Implications of this scenario for Mercury's magnetic field strength and geometry need to be further examined.
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Direct observation of terahertz surface modes in nanometer-sized liquid water pools.
Boyd, J E; Briskman, A; Colvin, V L; Mittleman, D M
2001-10-01
The far-infrared absorption spectrum of nanometer-sized water pools at the core of AOT micelles exhibits a pronounced resonance which is absent in bulk water. The amplitude and spectral position of this resonance are sensitive to the size of the confined water core. This resonance results from size-dependent modifications in the vibrational density of states, and thus has far-reaching implications for chemical processes which involve water sequestered within small cavities. These data represent the first study of the terahertz dielectric properties of confined liquids.
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NASA Technical Reports Server (NTRS)
Kennedy, G. C.; Higgins, G. H.
1973-01-01
Rebuttal of suggestions from various critics attempting to provide an escape from the seeming paradox originated by Higgins and Kennedy's (1971) proposed possibility that the liquid in the outer core was thermally stably stratified and that this stratification might prove a powerful inhibitor to circulation of the outer core fluid of the kind postulated for the generation of the earth's magnetic field. These suggestions are examined and shown to provide no reasonable escape from the core paradox.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hoshino, K.; Kameyama, Y.
1988-03-01
Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopesmore » of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ai, H; Zhang, H
Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant thatmore » represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.« less
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Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells
Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh
2017-01-01
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication. PMID:28423495
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Luo, Judong; Zhu, Wei; Tang, Yiting; Cao, Han; Zhou, Yuanyuan; Ji, Rong; Zhou, Xifa; Lu, Zhongkai; Yang, Hongying; Zhang, Shuyu; Cao, Jianping
2014-03-25
Cervical cancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown radiosensitization effect in previous studies. However, such effects of ART have not yet been revealed for cervical cancer cells. The effect of ART on radiosensitivity of human cervical cancer cell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. ART increased the radiosensitivity of HeLa cells (SER=1.43, P<0.001) but not of SiHa cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR+ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR+ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the G2/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. ART potently abrogates the G2 checkpoint control in HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo.
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Jin, Qiao; Li, Xiangjun; Cao, Peiguo
2015-10-01
This experiment was conducted to investigate the role of EPH receptor A2 (EphA2) in the modulation of radiosensitivity of hepatic cellular cancer (HCC) cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK) signaling mediated EphA2 function in this respect. The protein expressions of EphA2 and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA2 was overexpressed and knocked out by transfection with EphA2 expression vector and EphA2-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA2 and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy) only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively). However, EphA2 knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01). By contrast, EphA2 overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of radiosensitivity of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA2. The effect of EphA2 overexpression on the radiosensitivity of HCC 97H cells was abrogated. Thus, the present study indicates that EphA2 have the ability to negatively regulate the radiosensitivity of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways. Copyright © 2015. Published by Elsevier Taiwan.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Isebaert, Sofie F., E-mail: sofie.isebaert@med.kuleuven.be; Swinnen, Johannes V.; McBride, William H.
2011-09-01
Purpose: During the past decade, many clinical trials with both monoclonal antibodies and small molecules that target the insulin-like growth factor-type 1 receptor (IGF-1R) have been launched. Despite the important role of IGF-1R signaling in radioresistance, studies of such agents in combination with radiotherapy are lagging behind. Therefore, the aim of this study was to investigate the effect of the small molecule IGF-1R kinase inhibitor NVP-AEW541 on the intrinsic radioresistance of prostate cancer cells. Methods and Materials: The effect of NVP-AEW541 on cell proliferation, cell viability, IGF-1R signaling, radiosensitivity, cell cycle distribution, and double strand break repair was determined inmore » three human prostate cancer cell lines (PC3, DU145, 22Rv1). Moreover, the importance of the PTEN pathway status was explored by means of transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Results: NVP-AEW541 inhibited cell proliferation and decreased cell viability in a time-and dose-dependent manner in all three cell lines. Radiosensitization was observed in the PTEN wild-type cell lines DU145 and 22Rv1 but not in the PTEN-deficient PC3 cell line. NVP-AEW541-induced radiosensitization coincided with downregulation of phospho-Akt levels and high levels of residual double strand breaks. The importance of PTEN status in the radiosensitization effect was confirmed by transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Conclusions: NVP-AEW541 enhances the effect of ionizing radiation in PTEN wild-type, but not in PTEN-deficient, prostate cancer cells. Proper patient selection based on the PTEN status of the tumor will be critical to the achievement of optimal results in clinical trials in which the combination of radiotherapy and this IGF-1R inhibitor is being explored.« less
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Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kleiman, Norman Jay
The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiationmore » exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9, influence cataract development and thus radiosensitivity. These observations have direct applicability to various human populations including accidentally exposed individuals, interventional medical workers, astronauts and nuclear plant workers.« less
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SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yan, D; Chen, S; Krauss, D
Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function ofmore » pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cowan, D.S.; Panicucci, R.; McClelland, R.A.
The nitroimidazole-linked phenanthridine series of compounds (NLP-1, 2, and 3) were synthesized under the assumption that it should be possible to enhance the molar efficiency of 2-nitroimidazoles as hypoxic cell radiosensitizers and cytotoxins by targeting them to their likely site of action, DNA. The targeting group chosen was the phenanthridine moiety, the major component of the classical DNA intercalating compound, ethidium bromide. The sole difference between the compounds is the length of the hydrocarbon chain linking the nitroimidazole to the phenanthridine. The phenanthridine group with a three-carbon side chain, P-1, was also synthesized to allow studies on the effect ofmore » the targeting group by itself. The ability of the compounds to bind to DNA is inversely proportional to their linker chain length with binding constant values ranging from approximately 1 {times} 10(5) mol-1 for NLP-2 to 6 {times} 10(5) mol-1 for NLP-3. The NLP compounds show selective toxicity to hypoxic cells at 37 degrees C at external drug concentrations 10-40 times lower than would be required for untargeted 2-nitroimidazoles such as misonidazole in vitro. Toxicity to both hypoxic and aerobic cells is dependent on the linker chain: the shorter the chain, the greater the toxicity. In addition, the NLP compounds radiosensitize hypoxic cells at external drug concentrations as low as 0.05 mM with almost the full oxygen effect being observed at a concentration of 0.5 mM. These concentrations are 10-100 times lower than would be required for similar radiosensitization using misonidazole. Radiosensitizing ability is independent of linker chain length. The present compounds represent prototypes for further studies of the efficacy and mechanism of action of 2-nitroimidazoles targeted to DNA by linkage to an intercalating group.« less
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Cell-specific radiosensitization by gold nanoparticles at megavoltage radiation energies.
Jain, Suneil; Coulter, Jonathan A; Hounsell, Alan R; Butterworth, Karl T; McMahon, Stephen J; Hyland, Wendy B; Muir, Mark F; Dickson, Glenn R; Prise, Kevin M; Currell, Fred J; O'Sullivan, Joe M; Hirst, David G
2011-02-01
Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies. Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin. GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38). We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization. Copyright © 2011 Elsevier Inc. All rights reserved.
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Mbah, Chamberlain; De Ruyck, Kim; De Schrijver, Silke; De Sutter, Charlotte; Schiettecatte, Kimberly; Monten, Chris; Paelinck, Leen; De Neve, Wilfried; Thierens, Hubert; West, Catharine; Amorim, Gustavo; Thas, Olivier; Veldeman, Liv
2018-05-01
Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB2 rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with radiosensitivity, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall radiosensitivity. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient characteristics that are associated with radiosensitivity were identified without explicitly quantifying radiosensitivity.
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Permeability of sediment cores from methane hydrate deposit in the Eastern Nankai Trough, Japan
NASA Astrophysics Data System (ADS)
Konno, Y.; Yoneda, J.; Egawa, K.; Ito, T.; Jin, Y.; Kida, M.; Suzuki, K.; Nakatsuka, Y.; Nagao, J.
2013-12-01
Effective and absolute permeability are key parameters for gas production from methane-hydrate-bearing sandy sediments. Effective and/or absolute permeability have been measured using methane-hydrate-bearing sandy cores and clayey and silty cores recovered from Daini Atsumi Knoll in the Eastern Nankai Trough during the 2012 JOGMEC/JAPEX Pressure coring operation. Liquid-nitrogen-immersed cores were prepared by rapid depressurization of pressure cores recovered by a pressure coring system referred to as the Hybrid PCS. Cores were shaped cylindrically on a lathe with spraying of liquid nitrogen to prevent hydrate dissociation. Permeability was measured by a flooding test or a pressure relaxation method under near in-situ pressure and temperature conditions. Measured effective permeability of hydrate-bearing sediments is less than tens of md, which are order of magnitude less than absolute permeability. Absolute permeability of clayey cores is approximately tens of μd, which would perform a sealing function as cap rocks. Permeability reduction due to a swelling effect was observed for a silty core during flooding test of pure water mimicking hydrate-dissociation-water. Swelling effect may cause production formation damage especially at a later stage of gas production from methane hydrate deposits. This study was financially supported by the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) that carries out Japan's Methane Hydrate R&D Program conducted by the Ministry of Economy, Trade and Industry (METI).
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Thermodynamics and Equations of State of Iron to 350 GPa and 6000 K
NASA Astrophysics Data System (ADS)
Dorogokupets, P. I.; Dymshits, A. M.; Litasov, K. D.; Sokolova, T. S.
2017-03-01
The equations of state for solid (with bcc, fcc, and hcp structures) and liquid phases of Fe were defined via simultaneous optimization of the heat capacity, bulk moduli, thermal expansion, and volume at room and higher temperatures. The calculated triple points at the phase diagram have the following parameters: bcc-fcc-hcp is located at 7.3 GPa and 820 K, bcc-fcc-liquid at 5.2 GPa and 1998 K, and fcc-hcp-liquid at 106.5 GPa and 3787 K. At conditions near the fcc-hcp-liquid triple point, the Clapeyron slope of the fcc-liquid curve is dT/dP = 12.8 K/GPa while the slope of the hcp-liquid curve is higher (dT/dP = 13.7 K/GPa). Therefore, the hcp-liquid curve overlaps the metastable fcc-liquid curve at pressures of about 160 GPa. At high-pressure conditions, the metastable bcc-hcp curve is located inside the fcc-Fe or liquid stability field. The density, adiabatic bulk modulus and P-wave velocity of liquid Fe calculated up to 328.9 GPa at adiabatic temperature conditions started from 5882 K (outer/inner core boundary) were compared to the PREM seismological model. We determined the density deficit of hcp-Fe at the inner core boundary (T = 5882 K and P = 328.9 GPa) to be 4.4%.
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Thermodynamics and Equations of State of Iron to 350 GPa and 6000 K.
Dorogokupets, P I; Dymshits, A M; Litasov, K D; Sokolova, T S
2017-03-06
The equations of state for solid (with bcc, fcc, and hcp structures) and liquid phases of Fe were defined via simultaneous optimization of the heat capacity, bulk moduli, thermal expansion, and volume at room and higher temperatures. The calculated triple points at the phase diagram have the following parameters: bcc-fcc-hcp is located at 7.3 GPa and 820 K, bcc-fcc-liquid at 5.2 GPa and 1998 K, and fcc-hcp-liquid at 106.5 GPa and 3787 K. At conditions near the fcc-hcp-liquid triple point, the Clapeyron slope of the fcc-liquid curve is dT/dP = 12.8 K/GPa while the slope of the hcp-liquid curve is higher (dT/dP = 13.7 K/GPa). Therefore, the hcp-liquid curve overlaps the metastable fcc-liquid curve at pressures of about 160 GPa. At high-pressure conditions, the metastable bcc-hcp curve is located inside the fcc-Fe or liquid stability field. The density, adiabatic bulk modulus and P-wave velocity of liquid Fe calculated up to 328.9 GPa at adiabatic temperature conditions started from 5882 K (outer/inner core boundary) were compared to the PREM seismological model. We determined the density deficit of hcp-Fe at the inner core boundary (T = 5882 K and P = 328.9 GPa) to be 4.4%.
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Thermodynamics and Equations of State of Iron to 350 GPa and 6000 K
Dorogokupets, P. I.; Dymshits, A. M.; Litasov, K. D.; Sokolova, T. S.
2017-01-01
The equations of state for solid (with bcc, fcc, and hcp structures) and liquid phases of Fe were defined via simultaneous optimization of the heat capacity, bulk moduli, thermal expansion, and volume at room and higher temperatures. The calculated triple points at the phase diagram have the following parameters: bcc–fcc–hcp is located at 7.3 GPa and 820 K, bcc–fcc–liquid at 5.2 GPa and 1998 K, and fcc–hcp–liquid at 106.5 GPa and 3787 K. At conditions near the fcc–hcp–liquid triple point, the Clapeyron slope of the fcc–liquid curve is dT/dP = 12.8 K/GPa while the slope of the hcp–liquid curve is higher (dT/dP = 13.7 K/GPa). Therefore, the hcp–liquid curve overlaps the metastable fcc–liquid curve at pressures of about 160 GPa. At high-pressure conditions, the metastable bcc–hcp curve is located inside the fcc-Fe or liquid stability field. The density, adiabatic bulk modulus and P-wave velocity of liquid Fe calculated up to 328.9 GPa at adiabatic temperature conditions started from 5882 K (outer/inner core boundary) were compared to the PREM seismological model. We determined the density deficit of hcp-Fe at the inner core boundary (T = 5882 K and P = 328.9 GPa) to be 4.4%. PMID:28262683
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Hydrocolloid liquid-core capsules for the removal of heavy-metal cations from water.
Nussinovitch, A; Dagan, O
2015-12-15
Liquid-core capsules with a non-crosslinked alginate fluidic core surrounded by a gellan membrane were produced in a single step to investigate their ability to adsorb heavy metal cations. The liquid-core gellan-alginate capsules, produced by dropping alginate solution with magnesium cations into gellan solution, were extremely efficient at adsorbing lead cations (267 mg Pb(2+)/g dry alginate) at 25 °C and pH 5.5. However, these capsules were very weak and brittle, and an external strengthening capsule was added by using magnesium cations. The membrane was then thinned with the surfactant lecithin, producing capsules with better adsorption attributes (316 mg Pb(+2)/g dry alginate vs. 267 mg Pb(+2)/g dry alginate without lecithin), most likely due to the thinner membrane and enhanced mass transfer. The capsules' ability to adsorb other heavy-metal cations - copper (Cu(2+)), cadmium (Cd(2+)) and nickel (Ni(2+)) - was tested. Adsorption efficiencies were 219, 197 and 65 mg/g, respectively, and were correlated with the cation's affinity to alginate. Capsules with the sorbed heavy metals were regenerated by placing in a 1M nitric acid suspension for 24h. Capsules could undergo three regeneration cycles before becoming damaged. Copyright © 2015 Elsevier B.V. All rights reserved.
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Complementary high performance sensing of gases and liquids using silver nanotube
NASA Astrophysics Data System (ADS)
Isro, Suhandoko D.; Iskandar, Alexander A.; Tjia, May-On
2017-11-01
A study on refractive index sensing using a silver nanotube is carried out to investigate the relative advantages of sensing gaseous and liquid samples outside the tube (outer sensing) and inside the core (inner sensing). The geometrical and material parameters of the nanotube are varied to explore the favorable sensing performances covering the range of refractive indices between 1.1 and 1.5. It is shown that the performances at the three sensing points considered are consistently improved with decreased shell thickness and core radius in both sensing modes. While the performance is also monotonously and drastically enhanced with decreased counter permittivity in inner sensing, the similarly large variations in the outer sensing mode are less than strictly consistent. The study further shows that the most favorable FOM values are attained by both sensing modes with 2.5 nm Ag shell thickness and 27.5 nm core radius of the nanotube, whereas the most favorable counter permittivities are different for the two modes. Remarkably, the trend of increasing FOM for samples of lower refractive indices in outer sensing is entirely reversed in inner sensing with roughly the same level of performances. Thus, the core/shell structure of the silver nanotube offers the complementary high performance sensing of gases and liquids using the two sensing modes with appropriately chosen system parameters.
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Wang, Yongmei; Yang, Chongchong; Sun, Yan; Qiu, Fengtao; Xiang, Yang; Fu, Guoqi
2018-02-01
Surface molecular imprinting over functionalized nanoparticles has proved to be an effective approach for construction of artificial nanomaterials for protein recognition. Herein, we report a strategy for synthesis of core-shell protein-imprinted nanoparticles by the functionalization of nano-cores with ionic liquids followed by aqueous precipitation polymerization to build thermo-responsive imprinted polymer nano-shells. The immobilized ionic liquids can form multiple interactions with the protein template. The polymerization process can produce thermo-reversible physical crosslinks, which are advantageous to enhancing imprinting and facilitating template removal. With bovine hemoglobin as a model template, the imprinted nanoparticles showed temperature-sensitivity in both dispersion behaviors and rebinding capacities. Compared with the ionic-liquid-modified core nanoparticles, the imprinted particles exhibited greatly increased selectivity and two orders of magnitude higher binding affinity for the template protein. The imprinted nanoparticles achieved relatively high imprinting factor up to 5.0 and specific rebinding capacity of 67.7 mg/g, respectively. These nanoparticles also demonstrated rapid rebinding kinetics and good reproducibility after five cycles of adsorption-regeneration. Therefore, the presented approach may be viable for the fabrication of high-performance protein-imprinted nanoparticles with temperature sensitivity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Wu, Xiabing; You, Linjun; Di, Bin; Hao, Weiqiang; Su, Mengxiang; Gu, Yu; Shen, Lingling
2013-07-19
Novel chiral core-shell silica microspheres with trans-(1R,2R)-diaminocyclohexane (DACH) moiety bridged in the mesoporous shell were synthesized using layer-by-layer method. The chiral mesoporous shell around the nonporous silica core was formed by the co-condensation of N,N'-bis-[(triethoxysilyl)propyl]-trans-(1R,2R)-bis-(ureido)-cyclohexane (DACH-BS) and tetraethoxysilane (TEOS) using octadecyltrimethylammonium chloride (C18TMACl) and triblock poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) copolymer (P123) as the templates. The functionalized core-shell silica microspheres were characterized and tested as chiral stationary phases for high performance liquid chromatography (HPLC). R/S-1,1'-bi-2,2'-naphthol, R/S-6,6'-dibromo-1,1'-bi-2-naphthol and R/S-1,1'-bi-2,2'-phenanthrol were enantioseparated rapidly on the column packed with the DACH core-shell silica particles. Moreover, the column packed with core-shell particles exhibited better performance than the column packed with the DACH functionalized periodic mesoporous organosilicas. Copyright © 2013 Elsevier B.V. All rights reserved.
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2006-11-01
Technical Report 11 December 2005 - 30 November 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Nanoscale Ionic Liquids 5b. GRANT NUMBER FA9550-06-1-0012...Title: Nanoscale Ionic Liquids Principal Investigator: Emmanuel P. Giannelis Address: Materials Science and Engineering, Bard Hall, Cornell University...based fluids exhibit high ionic conductivity. The NFs are typically synthesized by grafting a charged, oligomeric corona onto the nanoparticle cores
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Vanhemmen, J.J.; Meuling, W.J.A.; Bleichrodt, J.F.
1974-01-01
The radiosensitization by oxygen of biological active bacteriophage DNA in bacterial extracts was studied. The oxygen effect in such a system appeared not to be due or due only to a minor extent to the presence of endogenous sulfhydryl compounds. The components in a cell extract which enable oxygen and other sensitizers to sensitize DNA could not be destroyed by extremely high doses of gamma radiation. (Author) (GRA)
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Radiosensitization of Hypoxic Tumor Cells by Depletion of Intracellular Glutathione
NASA Astrophysics Data System (ADS)
Bump, Edward A.; Yu, Ning Y.; Brown, J. Martin
1982-08-01
Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.
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Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bump, E.A.; Yu, N.Y.; Brown, J.M.
1982-08-06
Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.
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NASA Technical Reports Server (NTRS)
Bird, R. Keith; Hoffman, Eric K.
1998-01-01
The suitability of using transient liquid phase (TLP) bonding to fabricate honeycomb core sandwich panels with Ti-14Al-21Nb (wt%) titanium aluminide (T3Al) face sheets for high-temperature hypersonic vehicle applications was evaluated. Three titanium alloy honeycomb cores and one Ti3Al alloy honeycomb core were investigated. Edgewise compression (EWC) and flatwise tension (FWT) tests on honeycomb core sandwich specimens and tensile tests of the face sheet material were conducted at temperatures ranging from room temperature to 1500 F. EWC tests indicated that the honeycomb cores and diffusion bonded joints were able to stabilize the face sheets up to and beyond the face sheet compressive yield strength for all temperatures investigated. The specimens with the T3Al honeycomb core produced the highest FWT strengths at temperatures above 1000 F. Tensile tests indicated that TLP processing conditions resulted in decreases in ductility of the Ti-14Al-21Nb face sheets. Microstructural examination showed that the side of the face sheets to which the filler metals had been applied was transformed from equiaxed alpha2 grains to coarse plates of alpha2 with intergranular Beta. Fractographic examination of the tensile specimens showed that this transformed region was dominated by brittle fracture.
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Lin, Wei-Shao; Ercoli, Carlo; Feng, Changyong; Morton, Dean
2012-07-01
The objective of this study was to compare the effect of veneering porcelain (monolithic or bilayer specimens) and core fabrication technique (heat-pressed or CAD/CAM) on the biaxial flexural strength and Weibull modulus of leucite-reinforced and lithium-disilicate glass ceramics. In addition, the effect of veneering technique (heat-pressed or powder/liquid layering) for zirconia ceramics on the biaxial flexural strength and Weibull modulus was studied. Five ceramic core materials (IPS Empress Esthetic, IPS Empress CAD, IPS e.max Press, IPS e.max CAD, IPS e.max ZirCAD) and three corresponding veneering porcelains (IPS Empress Esthetic Veneer, IPS e.max Ceram, IPS e.max ZirPress) were selected for this study. Each core material group contained three subgroups based on the core material thickness and the presence of corresponding veneering porcelain as follows: 1.5 mm core material only (subgroup 1.5C), 0.8 mm core material only (subgroup 0.8C), and 1.5 mm core/veneer group: 0.8 mm core with 0.7 mm corresponding veneering porcelain with a powder/liquid layering technique (subgroup 0.8C-0.7VL). The ZirCAD group had one additional 1.5 mm core/veneer subgroup with 0.7 mm heat-pressed veneering porcelain (subgroup 0.8C-0.7VP). The biaxial flexural strengths were compared for each subgroup (n = 10) according to ISO standard 6872:2008 with ANOVA and Tukey's post hoc multiple comparison test (p≤ 0.05). The reliability of strength was analyzed with the Weibull distribution. For all core materials, the 1.5 mm core/veneer subgroups (0.8C-0.7VL, 0.8C-0.7VP) had significantly lower mean biaxial flexural strengths (p < 0.0001) than the other two subgroups (subgroups 1.5C and 0.8C). For the ZirCAD group, the 0.8C-0.7VL subgroup had significantly lower flexural strength (p= 0.004) than subgroup 0.8C-0.7VP. Nonetheless, both veneered ZirCAD groups showed greater flexural strength than the monolithic Empress and e.max groups, regardless of core thickness and fabrication techniques. Comparing fabrication techniques, Empress Esthetic/CAD, e.max Press/CAD had similar biaxial flexural strength (p= 0.28 for Empress pair; p= 0.87 for e.max pair); however, e.max CAD/Press groups had significantly higher flexural strength (p < 0.0001) than Empress Esthetic/CAD groups. Monolithic core specimens presented with higher Weibull modulus with all selected core materials. For the ZirCAD group, although the bilayer 0.8C-0.7VL subgroup exhibited significantly lower flexural strength, it had highest Weibull modulus than the 0.8C-0.7VP subgroup. The present study suggests that veneering porcelain onto a ceramic core material diminishes the flexural strength and the reliability of the bilayer specimens. Leucite-reinforced glass-ceramic cores have lower flexural strength than lithium-disilicate ones, while fabrication techniques (heat-pressed or CAD/CAM) and specimen thicknesses do not affect the flexural strength of all glass ceramics. Compared with the heat-pressed veneering technique, the powder/liquid veneering technique exhibited lower flexural strength but increased reliability with a higher Weibull modulus for zirconia bilayer specimens. Zirconia-veneered ceramics exhibited greater flexural strength than monolithic leucite-reinforced and lithium-disilicate ceramics regardless of zirconia veneering techniques (heat-pressed or powder/liquid technique). © 2012 by the American College of Prosthodontists.
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Inflation of a magma chamber surrounded by poroelastic mush shell
NASA Astrophysics Data System (ADS)
Liao, Y.; Soule, S. A.; Jones, M.
2017-12-01
Recent studies have highlighted the importance of crystal-rich mush in crustal magmatic system [Cashman et. al. 2017]. This potential paradigm shift from isolated melt bodies in elastic crust poses new challenges to our previous understanding of igneous processes. Existing models describing the physical processes in a conventional magma plumbing system may require modification to account for the properties of mush. In this study, we demonstrate that the abundance of very crystalline mush between magma lenses and the crustal rocks influences the mechanical coupling between pressurized magma lenses and their surroundings with regard to deformation and melt transport. We develop a conceptual model invoking a simplified geometry and presumed rheological properties of liquid magma, mush and country rock. In our preliminary study, a magma chamber is modeled as a spherical liquid core enveloped by a shell of poroelastic, magma-(and/or)-gas-bearing mush in an infinite domain of elastic country rock. We interrogate the effect of varying physical properties of the system (e.g., geometry) and mush material (e.g., elastic moduli) on the deformation in the liquid core, mush shell and host rock, as well as pressure built-up in the chamber, upon injection of magma into the liquid core. When we allow the pore spaces to be connected in the mush shell, melt can migrate within the permeable matrix, thereby promoting melt segregation or `leaking' from the core to the shell. These initial results highlight the importance of constraining the physical properties of crystal mush in order for us to properly evaluate the mechanics of magmatic system.
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NASA Astrophysics Data System (ADS)
Furusawa, Shun; Sumiyoshi, Kohsuke; Yamada, Shoichi; Suzuki, Hideyuki
2013-08-01
We construct new equations of state for baryons at subnuclear densities for the use in core-collapse simulations of massive stars. The abundance of various nuclei is obtained together with thermodynamic quantities. A model free energy is constructed, based on the relativistic mean field theory for nucleons and the mass formula for nuclei with the proton number up to ~1000. The formulation is an extension of the previous model, in which we adopted the liquid drop model to all nuclei under the nuclear statistical equilibrium. We reformulate the new liquid drop model so that the temperature dependences of bulk energies could be taken into account. Furthermore, we extend the region in the nuclear chart, in which shell effects are included, by using theoretical mass data in addition to experimental ones. We also adopt a quantum-theoretical mass evaluation of light nuclei, which incorporates the Pauli- and self-energy shifts that are not included in the ordinary liquid drop model. The pasta phases for heavy nuclei are taken into account in the same way as in the previous model. We find that the abundances of heavy nuclei are modified by the shell effects of nuclei and temperature dependence of bulk energies. These changes may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. The abundances of light nuclei are also modified by the new mass evaluation, which may affect the heating and cooling rates of supernova cores and shocked envelopes.
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Stokes-Einstein relation in liquid iron-nickel alloy up to 300 GPa
NASA Astrophysics Data System (ADS)
Cao, Q.-L.; Wang, P.-P.
2017-05-01
Molecular dynamic simulations were applied to investigate the Stokes-Einstein relation (SER) and the Rosenfeld entropy scaling law (ESL) in liquid Fe0.9Ni0.1 over a sufficiently broad range of temperatures (0.70 < T/Tm < 1.85 Tm is melting temperature) and pressures (from 50 GPa to 300 GPa). Our results suggest that the SER and ESL hold well in the normal liquid region and break down in the supercooled region under high-pressure conditions, and the deviation becomes larger with decreasing temperature. In other words, the SER can be used to calculate the viscosity of liquid Earth's outer core from the self-diffusion coefficients of iron/nickel and the ESL can be used to predict the viscosity and diffusion coefficients of liquid Earth's outer core form its structural properties. In addition, the pressure dependence of effective diameters cannot be ignored in the course of using the SER. Moreover, ESL provides a useful, structure-based probe for the validity of SER, while the ratio of the self-diffusion coefficients of the components cannot be used as a probe for the validity of SER.
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Breakup phenomena of a coaxial jet in the non-dilute region using real-time X-ray radiography
NASA Astrophysics Data System (ADS)
Cheung, F. B.; Kuo, K. K.; Woodward, R. D.; Garner, K. N.
1990-07-01
An innovative approach to the investigation of liquid jet breakup processes in the near-injector region has been developed to overcome the experimental difficulties associated with optically opaque, dense sprays. Real-time X-ray radiography (RTR) has been employed to observe the inner structure and breakup phenomena of coaxial jets. In the atomizing regime, droplets much smaller than the exit diameter are formed beginning essentially at the injector exit. Through the use of RTR, the instantaneous contour of the liquid core was visualized. Experimental results consist of controlled-exposure digital video images of the liquid jet breakup process. Time-averaged video images have also been recorded for comparison. A digital image processing system is used to analyze the recorded images by creating radiance level distributions of the jet. A rudimentary method for deducing intact-liquid-core length has been suggested. The technique of real-time X-ray radiography has been shown to be a viable approach to the study of the breakup processes of high-speed liquid jets.
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NASA Astrophysics Data System (ADS)
Shimoyama, Yuta; Terasaki, Hidenori; Ohtani, Eiji; Urakawa, Satoru; Takubo, Yusaku; Nishida, Keisuke; Suzuki, Akio; Katayama, Yoshinori
2013-11-01
Carbon is a plausible light element candidate in the Earth’s outer core. We measured the density of liquid Fe-3.5 wt% C up to 6.8 GPa and 2200 K using an X-ray absorption method. The compression curve of liquid Fe-C was fitted using the third-order Birch-Murnaghan equation of state. The bulk modulus and its pressure derivative are K0,1500K = 55.3 ± 2.5 GPa and (dK0/dP)T = 5.2 ± 1.5, and the thermal expansion coefficient is α = 0.86 ± 0.04 × 10-4 K-1. The Fe-C density abruptly increases at pressures between 4.3 and 5.5 GPa in the range of present temperatures. Compared with the results of previous density measurements of liquid Fe-C, the effect of carbon on the density of liquid Fe shows a nonideal mixing behavior. The abrupt density increase and nonideal mixing behavior are important factors in determining the light element content in the Earth’s core.
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Non-Abelian fractional quantum Hall states for hard-core bosons in one dimension
NASA Astrophysics Data System (ADS)
Paredes, Belén
2012-05-01
I present a family of one-dimensional bosonic liquids analogous to non-Abelian fractional quantum Hall states. A new quantum number is introduced to characterize these liquids, the chiral momentum, which differs from the usual angular or linear momentum in one dimension. As their two-dimensional counterparts, these liquids minimize a k-body hard-core interaction with the minimum total chiral momentum. They exhibit global order, with a hidden organization of the particles in k identical copies of a one-dimensional Laughlin state. For k=2 the state is a p-wave paired phase corresponding to the Pfaffian quantum Hall state. By imposing conservation of the total chiral momentum, an exact parent Hamiltonian is derived which involves long-range tunneling and interaction processes with an amplitude decaying with the chord distance. This family of non-Abelian liquids is shown to be in formal correspondence with a family of spin-(k)/(2) liquids which are total singlets made out of k indistinguishable resonating valence bond states. The corresponding spin Hamiltonians are obtained.
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Greco, Cristina; Marini, Alberto; Frezza, Elisa; Ferrarini, Alberta
2014-05-19
We present a computational investigation of the nematic phase of the bent-core liquid crystal A131. We use an integrated approach that bridges density functional theory calculations of molecular geometry and torsional potentials to elastic properties through the molecular conformational and orientational distribution function. This unique capability to simultaneously access different length scales enables us to consistently describe molecular and material properties. We can reassign (13)C NMR chemical shifts and analyze the dependence of phase properties on molecular shape. Focusing on the elastic constants we can draw some general conclusions on the unconventional behavior of bent-core nematics and highlight the crucial role of a properly-bent shape. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Core-Shell Columns in High-Performance Liquid Chromatography: Food Analysis Applications
Preti, Raffaella
2016-01-01
The increased separation efficiency provided by the new technology of column packed with core-shell particles in high-performance liquid chromatography (HPLC) has resulted in their widespread diffusion in several analytical fields: from pharmaceutical, biological, environmental, and toxicological. The present paper presents their most recent applications in food analysis. Their use has proved to be particularly advantageous for the determination of compounds at trace levels or when a large amount of samples must be analyzed fast using reliable and solvent-saving apparatus. The literature hereby described shows how the outstanding performances provided by core-shell particles column on a traditional HPLC instruments are comparable to those obtained with a costly UHPLC instrumentation, making this novel column a promising key tool in food analysis. PMID:27143972
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Thermal Modeling of the Injection of Standard and Thermally Insulated Cored Wire
NASA Astrophysics Data System (ADS)
Castro-Cedeno, E.-I.; Jardy, A.; Carré, A.; Gerardin, S.; Bellot, J. P.
2017-12-01
Cored wire injection is a widespread method used to perform alloying additions during ferrous and non-ferrous liquid metal treatment. The wire consists of a metal casing that is tightly wrapped around a core of material; the casing delays the release of the material as the wire is immersed into the melt. This method of addition presents advantages such as higher repeatability and yield of cored material with respect to bulk additions. Experimental and numerical work has been performed by several authors on the subject of alloy additions, spherical and cylindrical geometries being mainly considered. Surprisingly this has not been the case for cored wire, where the reported experimental or numerical studies are scarce. This work presents a 1-D finite volume numerical model aimed for the simulation of the thermal phenomena which occurs when the wire is injected into a liquid metal bath. It is currently being used as a design tool for the conception of new types of cored wire. A parametric study on the effect of injection velocity and steel casing thickness for an Al cored wire immersed into a steel melt at 1863 K (1590 °C) is presented. The standard single casing wire is further compared against a wire with multiple casings. Numerical results show that over a certain range of injection velocities, the core contents' release is delayed in the multiple casing when compared to a single casing wire.
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Coffinberry, A.S.
1962-04-10
A process for removing fission products from reactor liquid fuel without interfering with the reactor's normal operation or causing a significant change in its fuel composition is described. The process consists of mixing a liquid scavenger alloy composed of about 44 at.% plutoniunm, 33 at.% lanthanum, and 23 at.% nickel or cobalt with a plutonium alloy reactor fuel containing about 3 at.% lanthanum; removing a portion of the fuel and scavenger alloy from the reactor core and replacing it with an equal amount of the fresh scavenger alloy; transferring the portion to a quiescent zone where the scavenger and the plutonium fuel form two distinct liquid layers with the fission products being dissolved in the lanthanum-rich scavenger layer; and the clean plutonium-rich fuel layer being returned to the reactor core. (AEC)
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Tailoring sphere density for high pressure physical property measurements on liquids
NASA Astrophysics Data System (ADS)
Secco, R. A.; Tucker, R. F.; Balog, S. P.; Rutter, M. D.
2001-04-01
We present a new method of tailoring the density of a sphere for use as a probe in high pressure-temperature physical property experiments on liquids. The method consists of a composite sphere made of an inner, high density, metallic, spherical core and an exterior, low density, refractory, spherical shell or mantle. Micromechanical techniques are used to fabricate the composite sphere. We describe a relatively simple mechanical device that can grind hemispherical recesses as small as 200 μm in diameter in sapphire and as small as 500 μm in diameter in ruby hemispheres. Examples of composite spheres made with a Pt or WC core and Al2O3 shell used in metallic liquids pressurized to 16 GPa and 1900 K are shown.
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NASA Astrophysics Data System (ADS)
Lai, Xiaojing; Chen, Bin; Wang, Jianwei; Kono, Yoshio; Zhu, Feng
2017-12-01
During the formation of the Earth's core, the segregation of metallic liquids from silicate mantle should have left behind evident geochemical imprints on both the mantle and the core. Some distinctive geochemical signatures of the mantle-derived rocks likely own their origin to the metal-silicate differentiation of the primitive Earth, setting our planet apart from undifferentiated meteorites as well as terrestrial planets or moons isotopically and compositionally. Understanding the chemical evolution of terrestrial planetary bodies requires knowledge on properties of both liquid iron alloys and silicates equilibrating under physicochemical conditions pertinent to the deep magma ocean. Here we report experimental and computational results on the pressure-induced structural evolution of iron-nickel liquids alloyed with carbon. Our X-ray diffraction experiments up to 7.3 gigapascals (GPa) demonstrate that Fe-Ni (Fe90Ni10) liquids alloyed with 3 and 5 wt % carbon undergo a polyamorphic liquid structure transition at approximately 5 GPa. Corroborating the experimental observations, our first-principles molecular dynamic calculations reveal that the structural transitions result from the marked prevalence of three-atom face-sharing polyhedral connections in the liquids at >5 GPa. The structure and polyamorphic transitions of liquid iron-nickel-carbon alloys govern their physical and chemical properties and may thus cast fresh light on the chemical evolution of terrestrial planets and moons.
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Heinze, Brian C; Gamboa, Jessica R; Kim, Keesung; Song, Jae-Young; Yoon, Jeong-Yeol
2010-11-01
This work presents the use of integrated, liquid core, optical waveguides for measuring immunoagglutination-induced light scattering in a microfluidic device, towards rapid and sensitive detection of avian influenza (AI) viral antigens in a real biological matrix (chicken feces). Mie scattering simulations were performed and tested to optimize the scattering efficiency of the device through proper scatter angle waveguide geometry. The detection limit is demonstrated to be 1 pg mL(-1) in both clean buffer and real biological matrix. This low detection limit is made possible through on-chip diffusional mixing of AI target antigens and high acid content microparticle assay reagents, coupled with real-time monitoring of immunoagglutination-induced forward Mie scattering via high refractive index liquid core optical waveguides in close proximity (100 μm) to the sample chamber. The detection time for the assay is <2 min. This device could easily be modified to detect trace levels of any biological molecules that antibodies are available for, moving towards a robust platform for point-of-care disease diagnostics.
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Optofluidic waveguides: I. Concepts and implementations
Schmidt, Holger; Hawkins, Aaron R.
2011-01-01
We review recent developments and current status of liquid-core optical waveguides in optofluidics with emphasis on suitability for creating fully planar optofluidic labs-on-a-chip. In this first of two contributions, we give an overview of the different waveguide types that are being considered for effectively combining micro and nanofluidics with integrated optics. The large number of approaches is separated into conventional index-guided waveguides and more recent implementations using wave interference. The underlying principle for waveguiding and the current status are described for each type. We then focus on reviewing recent work on microfabricated liquid-core antiresonant reflecting optical (ARROW) waveguides, including the development of intersecting 2D waveguide networks and optical fluorescence and Raman detection with planar beam geometry. Single molecule detection capability and addition of electrical control for electrokinetic manipulation and analysis of single bioparticles are demonstrated. The demonstrated performance of liquid-core ARROWs is representative of the potential of integrated waveguides for on-chip detection with ultrahigh sensitivity, and points the way towards the next generation of high-performance, low-cost and portable biomedical instruments. PMID:21442048
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Biaxial order parameter in the homologous series of orthogonal bent-core smectic liquid crystals
NASA Astrophysics Data System (ADS)
Sreenilayam, S.; Panarin, Y. P.; Vij, J. K.; Osipov, M.; Lehmann, A.; Tschierske, C.
2013-07-01
The fundamental parameter of the uniaxial liquid crystalline state that governs nearly all of its physical properties is the primary orientational order parameter (S) for the long axes of molecules with respect to the director. The biaxial liquid crystals (LCs) possess biaxial order parameters depending on the phase symmetry of the system. In this paper we show that in the first approximation a biaxial orthogonal smectic phase can be described by two primary order parameters: S for the long axes and C for the ordering of the short axes of molecules. The temperature dependencies of S and C are obtained by the Haller's extrapolation technique through measurements of the optical birefringence and biaxiality on a nontilted polar antiferroelectric (Sm-APA) phase of a homologous series of LCs built from the bent-core achiral molecules. For such a biaxial smectic phase both S and C, particularly the temperature dependency of the latter, are being experimentally determined. Results show that S in the orthogonal smectic phase composed of bent cores is higher than in Sm-A calamatic LCs and C is also significantly large.
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Core Formation on Asteroid 4 Vesta: Iron Rain in a Silicate Magma Ocean
NASA Astrophysics Data System (ADS)
Kiefer, W. S.; Mittlefehldt, D. W.
2017-07-01
Initially small liquid metal drops must grow to about 10 cm in size before sinking through the convecting silicate magma ocean to form a core. The required magma temperature is consistent with moderately siderophile element abundances in eucrites.
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EXPERIMENTAL LIQUID METAL FUEL REACTOR
Happell, J.J.; Thomas, G.R.; Denise, R.P.; Bunts, J.L. Jr.
1962-01-23
A liquid metal fuel nuclear fission reactor is designed in which the fissionable material is dissolved or suspended in a liquid metal moderator and coolant. The liquid suspension flows into a chamber in which a critical amount of fissionable material is obtained. The fluid leaves the chamber and the heat of fission is extracted for power or other utilization. The improvement is in the support arrangement for a segrnented graphite core to permit dif ferential thermal expansion, effective sealing between main and blanket liquid metal flows, and avoidance of excessive stress development in the graphite segments. (AEC)
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Stevenson, D J
1981-11-06
Combined inferences from seismology, high-pressure experiment and theory, geomagnetism, fluid dynamics, and current views of terrestrial planetary evolution lead to models of the earth's core with the following properties. Core formation was contemporaneous with earth accretion; the core is not in chemical equilibrium with the mantle; the outer core is a fluid iron alloy containing significant quantities of lighter elements and is probably almost adiabatic and compositionally uniform; the more iron-rich inner solid core is a consequence of partial freezing of the outer core, and the energy release from this process sustains the earth's magnetic field; and the thermodynamic properties of the core are well constrained by the application of liquid-state theory to seismic and laboratory data.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gantt, R.; Sanford, K.K.; Parshad, R.
1987-03-01
A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containingmore » the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.« less
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Radiosensitivity and thermosensitization of thermotolerant Chinese hamster cells and RIF-1 tumors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hartson-Eaton, M.; Malcolm, A.W.; Hahn, G.M.
1984-07-01
CHO cells subline HA-1 were made thermotolerant by a priming heat treatment(43/sup 0/C, 30 min). Later, 4, 16, or 24 hr, they were either irradiated or heated (43/sup 0/C, 30 min) and irradiated. Thermotolerance had no effect on the radiation sensitivity of the cells as measured by the D/sub 0/ value of the clonogenic survival curve. However the N value of the curve (width of shoulder) showed a significant increase at 24 hr, indicating an increased capacity to accumulate sublethal damage. The same priming treatment was given to RIF-1 tumors growing in C3H mice. Later, 24 hr, when the tumorsmore » were either irradiated or heated (43/sup 0/C, 30 min) and irradiated, it was found that thermotolerance had no effect on the radiosensitivity of the cells as measured by in vitro assay. However, thermal radiosensitization was not apparent 24 hr after the priming treatment.« less
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[Radiotherapy and chaos theory: the tit bird and the butterfly...].
Denis, F; Letellier, C
2012-09-01
Although the same simple laws govern cancer outcome (cell division repeated again and again), each tumour has a different outcome before as well as after irradiation therapy. The linear-quadratic radiosensitivity model allows an assessment of tumor sensitivity to radiotherapy. This model presents some limitations in clinical practice because it does not take into account the interactions between tumour cells and non-tumoral bystander cells (such as endothelial cells, fibroblasts, immune cells...) that modulate radiosensitivity and tumor growth dynamics. These interactions can lead to non-linear and complex tumor growth which appears to be random but that is not since there is not so many tumors spontaneously regressing. In this paper we propose to develop a deterministic approach for tumour growth dynamics using chaos theory. Various characteristics of cancer dynamics and tumor radiosensitivity can be explained using mathematical models of competing cell species. Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.
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Liu, Yan; Zhang, Pengcheng; Li, Feifei; Jin, Xiaodong; Li, Jin; Chen, Weiqiang; Li, Qiang
2018-01-01
Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed. PMID:29556359
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Buchko, Garry W.; Weinfeld, Michael
The nitroimidazole-linked phenanthridines 2-NLP-3 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and 2-NLP-4 (5-[3-(2-nitro-1-imidazoyl)-butyl1]-phenanthridinium bromide) are composed of the radiosensitizer, 2-nitroimidazole, attached to the DNA intercalator phenanthridine via a 3- and 4-carbon linker, respectively. Previous in vitro assays show both compounds to be 10 - 100 times more efficient as hypoxic cell radiosensitizer, misonidazole[Cowan et al., Radiat. Res. 127, 81-89, 1991]. Here we have used a 32P postlabeling assay and 5'-end labeled oligonucleotide assay to compare the radiogenic DNA damage generated in the presence of 2-NLP-3, 2-NLP-4 compared to irradiation in the presence of misonidazole. This may account, at least in part, for the greatermore » cellular radiosensitization shown by the nitroimidazole-linked phenanthridines over misonidazole.« less
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NASA Astrophysics Data System (ADS)
Liu, Yingchao; Chen, Hailiang; Ma, Mingjian; Zhang, Wenxun; Wang, Yujun; Li, Shuguang
2018-03-01
We propose a tunable ultra-broadband polarization filter based on three-core resonance of the fluid-infiltrated and gold-coated high birefringent photonic crystal fiber (HB-PCF). Gold film was applied to the inner walls of two cladding air holes and surface plasmon polaritons were generated on its surface. The two gold-coated cladding air holes acted as two defective cores. As the phase matching condition was satisfied, light transmitted in the fiber core and coupled to the two defective cores. The three-core PCF supported three super modes in two orthogonal polarization directions. The coupling characteristics among these modes were investigated using the finite-element method. We found that the coupling wavelengths and strength between these guided modes can be tuned by altering the structural parameters of the designed HB-PCF, such as the size of the voids, thickness of the gold-films and liquid infilling pattern. Under the optimized structural parameters, a tunable broadband polarization filter was realized. For one liquid infilling pattern, we obtained a broadband polarization filter which filtered out the light in y-polarization direction at the wavelength of 1550 nm. For another liquid infilling pattern, we filtered out light in the x-polarization direction at the wavelength of 1310 nm. Our studies on the designed HB-PCF made contributions to the further devising of tunable broadband polarization filters, which are extensively used in telecommunication and sensor systems. Project supported by the National Natural Science Foundation of China (Grant Nos. 61505175 and 61475134) and the Natural Science Foundation of Hebei Province (Grant Nos. F2017203110 and F2017203193).
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Dynamic and magneto-optic properties of bent-core liquid crystals
NASA Astrophysics Data System (ADS)
Salili, Seyyed Muhammad
In this work, we describe dynamic behavior of free-standing bent-core liquid crystal filaments under dilative and axial compressive stresses in the B7 phase. We found that such filaments demonstrate very complex structures depending on the filament's temperature relative to the isotropic phase, initial filament thickness, and velocity at which the filament is pulled or compressed. We also present our experimental methods, results and analysis of the rupture and recoil properties of several bent-core liquid crystal filaments, anticipating that they may serve as a model system for complex biological fibers. After that, we systematically describe rheological measurements for dimeric liquid crystal compounds. We studied the shear-induced alignment properties, measured the viscoelastic properties as a function of temperature, shear rate, stress and frequency, and compared the results with the rheological properties of conventional chiral nematic and smectic phases. Then we present results of chiral nematic liquid crystals composed of flexible dimer molecules subject to large DC magnetic fields between 0 and 31T. We observe that these fields lead to selective reflection of light depending on temperature and magnetic field. The band of reflected wavelengths can be tuned from ultraviolet to beyond the IR-C band. A similar effect induced by electric fields has been presented previously, and was explained by a field-induced oblique-heliconical director deformation in accordance with early theoretical predictions. Finally, we report an unprecedented magnetic field-induced shifts of the isotropic-nematic phase transition temperature observed in liquid crystal dimers where two rigid linear mesogens are linked by flexible chains of either even- or odd-numbered hydrocarbon groups. This effect is explained in terms of quenching of the thermal fluctuations and decrease of the average bend angle of molecules in the odd-numbered dimers.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kwon, Jeanny; Kim, Dan Hyo; Park, Ji Min
Purpose: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti–hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. Methods and Materials: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed. Results: Of the 4 PI4K isotypes, specific inhibition of IIIα increased radiosensitivity. For pharmacologic inhibition of PI4K IIIα, we screened 9 anti-HCV agents by half-maximal inhibitorymore » concentration assay. Simeprevir was selected, and its inhibition of PI4K IIIα activity was confirmed. Combination of simeprevir treatment and radiation significantly attenuated expression of phospho-phospho-PKC and phospho-Akt and increased radiation-induced cell death in tested cell lines. Pretreatment with simeprevir prolonged γH2AX foci formation and down-regulation of phospho-DNA-PKcs, indicating impairment of nonhomologous end-joining repair. Cells pretreated with simeprevir exhibited mixed modes of cell death, including apoptosis and autophagy. Conclusion: These data demonstrate that targeting PI4K IIIα using an anti-HCV agent is a viable approach to enhance the therapeutic efficacy of radiation therapy in various human cancers, such as glioma, breast, and hepatocellular carcinoma.« less
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Inhibition of STAT-3 Results in Radiosensitization of Human Squamous Cell Carcinoma
Bonner, James A.; Trummell, Hoa Q.; Willey, Christopher D.; Plants, Brian A.; Raisch, Kevin P.
2009-01-01
Background Signal Transducer and Activator of Transcription – 3 (STAT-3) is a downstream component of the Epidermal Growth Factor Receptor (EGFr) signaling process that may facilitate the resistance of tumor cells to conventional cancer treatments. Studies were performed to determine if inhibition of this downstream protein may produce radiosensitization. Methods/Results A431 cells (human squamous cell carcinoma cells with EGFr overexpression) were found to be sensitized to radiation after treatment with STAT-3 small interfering RNA (siRNA). Therefore, a short hairpin RNA (shRNA) against STAT-3 was designed and cloned into a pBABE vector system modified for shRNA expression. Following transfection, clone 2.1 was selected for further study as it showed a dramatic reduction of STAT-3 protein (and mRNA) when compared to A431 parental cells or a negative control shRNA cell line (transfected with STAT-3 shRNA with 2 base pairs mutated). A431 2.1 showed doubling times of 25-31 h as compared to 18-24 h for the parental cell line. The A431 shRNA knockdown STAT-3 cells A431 were more sensitive to radiation than A431 parental or negative STAT-3 control cells. Conclusion A431 cells stably transfected with shRNA against STAT-3 resulted in enhanced radiosensitivity. Further work will be necessary to determine whether inhibition of STAT-3 phosphorylation is a necessary step for the radiosensitization that is induced by inhibition of EGFr. PMID:19616333
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Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng
2016-07-01
Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.
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Park, Yeunsoo; Polska, Katarzyna; Rak, Janusz; Wagner, J Richard; Sanche, Léon
2012-08-16
The replacement of nucleobases with brominated analogs enhances DNA radiosensitivity. We examine the chemistry of low-energy electrons (LEEs) in this sensitization process by experiments with thin films of the oligonucleotide trimers TBrXT, where BrX = 5-BrU (5-bromouracil), 5-BrC (5-bromocytosine), 8-BrA (8-bromoadenine), or 8-BrG (8-bromoguanine). The products induced from irradiation of thin (∼ 2.5 nm) oligonucleotide films, with 10 eV electrons, under ultrahigh vacuum (UHV) are analyzed by HPLC-UV. The number of damaged brominated trimers ranges from about 12 to 15 × 10(-3) molecules per incident electron, whereas under the identical conditions, these numbers drop to 4-7 × 10(-3) for the same, but nonbrominated oligonucleotides. The results of HPLC analysis show that the main degradation pathway of trinucleotides containing brominated bases involve debromination (i.e., loss of the bromine atom and its replacement with a hydrogen atom). The electron-induced sum of products upon bromination increases by factors of 2.1 for the pyrimidines and 3.2 for the purines. Thus, substitution of any native nucleobase with a brominated one in simple models of DNA increases LEE-induced damage to DNA and hence its radiosensitivity. Furthermore, besides the brominated pyrimidines that have already been tested in clinical trials, brominated purines not only appear to be promising sensitizers for radiotherapy, but could provide a higher degree of radiosensitization.
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Yan, Sen-Xiang; Luo, Xing-Mei; Zhou, Shui-Hong; Bao, Yang-Yang; Fan, Jun; Lu, Zhong-Jie; Liao, Xin-Biao; Huang, Ya-Ping; Wu, Ting-Ting; Wang, Qin-Ying
2013-01-01
Purpose: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. Methods: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. Results: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). Conclusion: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1. PMID:23983599
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NASA Astrophysics Data System (ADS)
Marrero, Carlos Sosa; Aubert, Vivien; Ciferri, Nicolas; Hernández, Alfredo; de Crevoisier, Renaud; Acosta, Oscar
2017-11-01
Understanding the response to irradiation in cancer radiotherapy (RT) may help devising new strategies with improved tumor local control. Computational models may allow to unravel the underlying radiosensitive mechanisms intervening in the dose-response relationship. By using extensive simulations a wide range of parameters may be evaluated providing insights on tumor response thus generating useful data to plan modified treatments. We propose in this paper a computational model of tumor growth and radiation response which allows to simulate a whole RT protocol. Proliferation of tumor cells, cell life-cycle, oxygen diffusion, radiosensitivity, RT response and resorption of killed cells were implemented in a multiscale framework. The model was developed in C++, using the Multi-formalism Modeling and Simulation Library (M2SL). Radiosensitivity parameters extracted from literature enabled us to simulate in a regular grid (voxel-wise) a prostate cell tissue. Histopathological specimens with different aggressiveness levels extracted from patients after prostatectomy were used to initialize in silico simulations. Results on tumor growth exhibit a good agreement with data from in vitro studies. Moreover, standard fractionation of 2 Gy/fraction, with a total dose of 80 Gy as a real RT treatment was applied with varying radiosensitivity and oxygen diffusion parameters. As expected, the high influence of these parameters was observed by measuring the percentage of survival tumor cell after RT. This work paves the way to further models allowing to simulate increased doses in modified hypofractionated schemes and to develop new patient-specific combined therapies.
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NASA Astrophysics Data System (ADS)
Abakumov, M. V.; Chechetkin, V. M.; Shalimov, S. L.
2018-05-01
The flow structure induced by thermal convection in a rotating spherical shell with viscous boundary conditions is considered under the assumption that the differential rotation of the core relative to the mantle is absent. The radial, azimuthal, and meridional components of the flow's velocity and helicity are studied. With the magnetic field assumed to be frozen into a liquid (frozen-flux hypothesis), it is shown that the numerical results fit the observations of the geomagnetic field variations close to the pole.
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Liquid-circulating garment controls thermal balance
NASA Technical Reports Server (NTRS)
Kuznetz, L. H.
1977-01-01
Experimental data and mathematical model of human thermoregulatory system have been used to investigate use of liquid-circulatory garment (LCG) to control thermal balance. Model proved useful as accurate simulator of such variables as sweat rate, skin temperature, core temperature, and radiative, evaporative, and LCG heat loss.
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Intensity liquid level sensor based on multimode interference and fiber Bragg grating
NASA Astrophysics Data System (ADS)
Oliveira, Ricardo; Aristilde, Stenio; Osório, Jonas H.; Franco, Marcos A. R.; Bilro, Lúcia; Nogueira, Rogério N.; Cordeiro, Cristiano M. B.
2016-12-01
In this paper an intensity liquid level sensor based on a single-mode—no-core—single-mode (SMS) fiber structure together with a Bragg grating inscribed in the later single mode fiber is proposed. As the no-core fiber is sensitive to the external refractive index, the SMS spectral response will be shifted related to the length of no-core fiber that is immersed in a liquid. By positioning the FBG central wavelength at the spectral region of the SMS edge filter, it is possible to measure the liquid level using the reflected FBG peak power through an intensity-based approach. The sensor is also self-referenced using the peak power of another FBG that is placed before and far from the sensing part. The temperature error analysis was also studied revealing that the sensor can operate in environments where the temperature changes are minimal. The possibility to use a second setup that makes the whole device temperature insensitive is also discussed.
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The Effect of Surface Topography on the Nonlinear Dynamics of Rossby Waves
NASA Technical Reports Server (NTRS)
Abarzhi, S. I.; Desjardins, O.; Pitsch, H.
2003-01-01
Boussinesq convection in rotating systems attracts a sustained attention of the fluid dynamics community, because it has intricate non-linear dynamics (Cross & Hohenberg 1993) and plays an important role in geophysical and astrophysical applications, such as the motion of the liquid outer core of Earth, the Red Spot in Jupiter, the giant cells in the Sun etc. (Alridge et al. 1990). A fundamental distinction between the real geo- and astrophysical problems and the idealized laboratory studies is that natural systems are inhomogeneous (Alridge et al. 1990). Heterogeneities modulate the flow and influence significantly the dynamics of convective patterns (Alridge et al. 1990; Hide 1971). The effect of modulations on pattern formation and transition to turbulence in Boussinesq convection is far from being completely understood (Cross & Hohenberg 1993; Aranson & Kramer 2002). It is generally accepted that in the liquid outer core of the Earth the transport of the angular momentum and internal heat occurs via thermal Rossby waves (Zhang et al. 2001; Kuang & Bloxham 1999). These waves been visualized in laboratory experiments in rotating liquid-filled spheres and concentric spherical shells (Zhang et al. 2001; Kuang & Bloxham 1999). The basic dynamical features of Rossby waves have been reproduced in a cylindrical annulus, a system much simpler than the spherical ones (Busse & Or 1986; Or & Busse 1987). For convection in a cylindrical annulus, the fluid motion is two-dimensional, and gravity is replaced by a centrifugal force, (Busse & Or 1986; Or & Busse 1987). Hide (1971) has suggested that the momentum and heat transport in the core might be influenced significantly by so-called bumps, which are heterogeneities on the mantle-core boundary. To model the effect of surface topography on the transport of momentum and energy in the liquid outer core of the Earth, Bell & Soward (1996), Herrmann & Busse (1998) and Westerburg & Busse (2001) have studied the nonlinear dynamics of thermal Rossby waves in a cylindrical annulus with azimuthally modulated height.
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Experimental evidence for Mo isotope fractionation between metal and silicate liquids
NASA Astrophysics Data System (ADS)
Hin, Remco C.; Burkhardt, Christoph; Schmidt, Max W.; Bourdon, Bernard; Kleine, Thorsten
2013-10-01
Stable isotope fractionation of siderophile elements may inform on the conditions and chemical consequences of core-mantle differentiation in planetary objects. The extent to which Mo isotopes fractionate during such metal-silicate segregation, however, is so far unexplored. We have therefore investigated equilibrium fractionation of Mo isotopes between liquid metal and liquid silicate to evaluate the potential of Mo isotopes as a new tool to study core formation. We have performed experiments at 1400 and 1600 °C in a centrifuging piston cylinder. Tin was used to lower the melting temperature of the Fe-based metal alloys to <1400 °C, while variable Fe-oxide contents were used to vary oxygen fugacity in graphite and MgO capsules. Isotopic analyses were performed using a double spike technique. In experiments performed at 1400 °C, the 98Mo/95Mo ratio of silicate is 0.19±0.03‰ (95% confidence interval) heavier than that of metal. This fractionation is not significantly affected by the presence or absence of carbon. Molybdenum isotope fractionation is furthermore independent of oxygen fugacity in the range IW -1.79 to IW +0.47, which are plausible values for core formation. Experiments at 1600 °C show that, at equilibrium, the 98Mo/95Mo ratio of silicate is 0.12±0.02‰ heavier than that of metal and that the presence or absence of Sn does not affect this fractionation. Equilibrium Mo isotope fractionation between liquid metal and liquid silicate as a function of temperature can therefore be described as ΔMoMetal-Silicate98/95=-4.70(±0.59)×105/T2. Our experiments show that Mo isotope fractionation may be resolvable up to metal-silicate equilibration temperatures of about 2500 °C, rendering Mo isotopes a novel tool to investigate the conditions of core formation in objects ranging from planetesimals to Earth sized bodies.
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Investigation of geomagnetic field forecasting and fluid dynamics of the core
NASA Technical Reports Server (NTRS)
Benton, E. R. (Principal Investigator)
1981-01-01
The magnetic determination of the depth of the core-mantle boundary using MAGSAT data is discussed. Refinements to the approach of using the pole-strength of Earth to evaluate the radius of the Earth's core-mantle boundary are reported. The downward extrapolation through the electrically conducting mantle was reviewed. Estimates of an upper bound for the time required for Earth's liquid core to overturn completely are presented. High order analytic approximations to the unsigned magnetic flux crossing the Earth's surface are also presented.
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Martan, T; Nemecek, T; Komanec, M; Ahmad, R; Zvanovec, S
2017-03-20
Detecting explosive, flammable, or toxic industrial liquids reliably and accurately is a matter of civic responsibility that cannot be treated lightly. Tapered optical fibers (TOFs) and suspended core microstructured optical fibers (SC MOFs) were separately used as sensors of liquids without being compared to each other. We present a highly sensitive time-stable TOF sensor incorporated in the pipeline system for the in-line regime of measurement. This paper is furthermore focused on the comparison of this TOF and SC MOF of similar parameters for the detection of selected liquids. A validated method that incorporates TOF and SC MOF of small core (waist) diameter for refractometric detection is presented. The principle of detection is based on the overlap of an enhanced evanescent wave with a liquid analyte that either fills the cladding holes of the SC MOF or surrounds the waist area of the TOF. Optical power within the evanescent wave for both sensing structures and selected liquid analytes is analyzed. Measurement results concerning TOF and SC MOF are compared. Calculations to ascertain the limit of detection (LOD) for each sensor and the sensitivity (S) to refractive indices of liquid analytes in the range of 1.4269 to 1.4361 were performed at a wavelength of 1550 nm with the lowest refractive index step of 0.0007. Results affirming that S=600.96 dB/RIU and LOD=0.0733 RIU for the SC MOF and S=1143.2 dB/RIU and LOD of 0.0026 RIU for the TOF sensor were achieved, clearly illustrating that TOF-based sensors can reach close to two times greater sensitivity and 30 times higher limit of detection. This paper extends the comparison of the fiber sensors by discussing the potential applications.
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Treshow, M.
1961-09-01
A boiling-water nuclear reactor is described wherein control is effected by varying the moderator-to-fuel ratio in the reactor core. This is accomplished by providing control tubes containing a liquid control moderator in the reactor core and providing means for varying the amount of control moderatcr within the control tubes.
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Radial blanket assembly orificing arrangement
Patterson, J.F.
1975-07-01
A nuclear reactor core for a liquid metal cooled fast breeder reactor is described in which means are provided for increasing the coolant flow through the reactor fuel assemblies as the reactor ages by varying the coolant flow rate with the changing coolant requirements during the core operating lifetime. (auth)
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Hurwitz, H. Jr.; Brooks, H.; Mannal, C.; Payne, J.H.; Luebke, E.A.
1959-03-24
A reactor of the heterogeneous, liquid cooled type is described. This reactor is comprised of a central region of a plurality of vertically disposed elongated tubes surrounded by a region of moderator material. The central region is comprised of a central core surrounded by a reflector region which is surrounded by a fast neutron absorber region, which in turn is surrounded by a slow neutron absorber region. Liquid sodium is used as the primary coolant and circulates through the core which contains the fuel elements. Control of the reactor is accomplished by varying the ability of the reflector region to reflect neutrons back into the core of the reactor. For this purpose the reflector is comprised of moderator and control elements having varying effects on reactivity, the control elements being arranged and actuated by groups to give regulation, shim, and safety control.
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Microencapsulation of gallium-indium (Ga-In) liquid metal for self-healing applications.
Blaiszik, B J; Jones, A R; Sottos, N R; White, S R
2014-01-01
Microcapsules containing a liquid metal alloy core of gallium-indium (Ga-In) are prepared via in situ urea-formaldehyde (UF) microencapsulation. The capsule size, shape, thermal properties, and shell wall thickness are investigated. We prepare ellipsoidal capsules with major and minor diameter aspect ratios ranging from 1.64 to 1.08 and with major diameters ranging from 245 µm to 3 µm. We observe that as the capsule major diameter decreases, the aspect ratio approaches 1. The thermal properties of the prepared microcapsules are investigated by thermogravimetric (TGA) and differential scanning calorimetry (DSC). Microcapsules are shown to survive incorporation into an epoxy matrix and to trigger via mechanical damage to the cured matrix. Microcapsules containing liquid metal cores may have diverse applications ranging from self-healing to contrast enhancement or the demonstration of mechano-adaptive circuitry.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Josephson, J.; Sowa, E.S.
1977-04-01
The design and testing of a simple and reliable Self-Actuated Shutdown System (SASS) for the protection of Liquid Metal Fast Breeder Reactors (LMFBRs) is described. A ferromagnetic Curie temperature permanent magnet holding device has been selected for the design of the Self-Actuated Shutdown System in order to enhance the safety of liquid metal cooled fast reactors (LMFBRs). The self-actuated, self-contained device operates such that accident conditions, resulting in increased coolant temperature or neutron flux reduce the magnetic holding force suspending a neutron absorber above the core by raising the temperature of the trigger mechanism above the Curie point. Neutron absorbermore » material is then inserted into the core, under gravity, terminating the accident. Two possible design variations of the selected concept are presented.« less
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Computational model for living nematic
NASA Astrophysics Data System (ADS)
Genkin, Mikhail; Sokolov, Andrey; Lavrentovich, Oleg; Aranson, Igor
A realization of an active system has been conceived by combining swimming bacteria and a lyotropic nematic liquid crystal. Here, by coupling the well-established and validated model of nematic liquid crystals with the bacterial dynamics we developed a computational model describing intricate properties of such a living nematic. In faithful agreement with the experiment, the model reproduces the onset of periodic undulation of the nematic director and consequent proliferation of topological defects with the increase in bacterial concentration. It yields testable prediction on the accumulation and transport of bacteria in the cores of +1/2 topological defects and depletion of bacteria in the cores of -1/2 defects. Our new experiment on motile bacteria suspended in a free-standing liquid crystalline film fully confirmed this prediction. This effect can be used to capture and manipulation of small amounts of bacteria.
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Linear and nonlinear dynamics of liquid planetary cores
NASA Astrophysics Data System (ADS)
Lathrop, D. P.
2013-12-01
This is the 50th anniversary of Ed Lorenz brilliant paper "Deterministic Nonperiodic Flow.'' Lorenz's work, along with many other founders' efforts, gave rise to the study of nonlinear dynamics. That field has allowed us to move beyond simple linear characterizations of nature, and to open up a deeper understanding of the Earth, other planets, and stars. Of the many things that make the Earth a habitable home, one is the existence of a planetary magnetic field generated in our liquid iron outer core. The generation process is known to be strongly nonlinear, and thereby almost certainly turbulent. Yet it is not a simple homogeneous isotropic turbulent flow, but is instead heavily modified by rotation and magnetic forces. We attempt to better understand the Earth's core using a three-meter liquid sodium laboratory model of the core. Our work in sodium in this system has just begun. The system exhibits a variety of behaviors with at least twelve different states, drawing different amounts of power, and causing varying levels of magnetic field amplification. In some states, rotation and magnetic fields cause the dynamics to simplify relative to more general turbulent flows in comparable conditions. Acknowledgements: I gratefully acknowledge my collaborators Daniel Zimmerman, Santiago Triana, Donald Martin, Nolan Balew, Henri-Claude Nataf, and Barbara Brawn-Cinani, and funding from the National Science Foundation Earth Sciences Instrumentation and Geophysics programs.
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Subcritical Thermal Convection of Liquid Metals in a Rapidly Rotating Sphere
NASA Astrophysics Data System (ADS)
Kaplan, E. J.; Schaeffer, N.; Vidal, J.; Cardin, P.
2017-09-01
Planetary cores consist of liquid metals (low Prandtl number Pr) that convect as the core cools. Here, we study nonlinear convection in a rotating (low Ekman number Ek) planetary core using a fully 3D direct numerical simulation. Near the critical thermal forcing (Rayleigh number Ra), convection onsets as thermal Rossby waves, but as Ra increases, this state is superseded by one dominated by advection. At moderate rotation, these states (here called the weak branch and strong branch, respectively) are smoothly connected. As the planetary core rotates faster, the smooth transition is replaced by hysteresis cycles and subcriticality until the weak branch disappears entirely and the strong branch onsets in a turbulent state at Ek <10-6. Here, the strong branch persists even as the thermal forcing drops well below the linear onset of convection (Ra =0.7 Racrit in this study). We highlight the importance of the Reynolds stress, which is required for convection to subsist below the linear onset. In addition, the Péclet number is consistently above 10 in the strong branch. We further note the presence of a strong zonal flow that is nonetheless unimportant to the convective state. Our study suggests that, in the asymptotic regime of rapid rotation relevant for planetary interiors, thermal convection of liquid metals in a sphere onsets through a subcritical bifurcation.
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Periodicity of the density wake past a vortex ring in a stratified liquid
NASA Astrophysics Data System (ADS)
Prokhorov, V.
2009-04-01
Spatial coherent structure of the density wake past a vortex ring moving horizontally in viscid stratified liquid is experimentally revealed. It follows from analysis that repetition period of the structure is determined by rotation radial frequency (or mean vorticity) of the vortex core and toward speed of the vortex ring. The wake formation of the ring is considered in respect to vorticity shedding which produces velocity disturbances in ambient medium. In case of stratified liquid velocity fluctuations, in their turn, cause density field distortion. This process is superimposed by vortex core oscillations, and, in result, vorticity shedding will be not monotonous but modulated at some frequency. So, the density wake is periodically structured, and the spatial period is defined by intrinsic frequency of the core and forward speed of the ring. To support analysis, experiments were conducted in which vortex rings excited by spring-piston generator were observed with high-sensitive Schlieren instrument and computer-controlled camera. Experimental tank was filled with salt-stratified water of constant buoyancy period, vortex ring velocities range from 3 to 16 cm/s. Spatial period is derived from schlieren image using two independent methods, both 2D spectral analysis and geometry calculations of the vortex core. Spatial periods and vortex intrinsic frequencies calculated by both algorithms are in good agreement; they vary in power lows depending on vortex speed
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Olvera-Trejo, D; Velásquez-García, L F
2016-10-18
This study reports the first MEMS multiplexed coaxial electrospray sources in the literature. Coaxial electrospraying is a microencapsulation technology based on electrohydrodynamic jetting of two immiscible liquids, which allows precise control with low size variation of the geometry of the core-shell particles it generates, which is of great importance in numerous biomedical and engineering applications, e.g., drug delivery and self-healing composites. By implementing monolithic planar arrays of miniaturized coaxial electrospray emitters that work uniformly in parallel, the throughput of the compound microdroplet source is greatly increased, making the microencapsulation technology compatible with low-cost commercial applications. Miniaturized core-shell particle generators with up to 25 coaxial electrospray emitters (25 emitters cm -2 ) were fabricated via stereolithography, which is an additive manufacturing process that can create complex microfluidic devices at a small fraction of the cost per device and fabrication time associated with silicon-based counterparts. The characterization of devices with the same emitter structure but different array sizes demonstrates uniform array operation. Moreover, the data demonstrate that the per-emitter current is approximately proportional to the square root of the flow rate of the driving liquid, and it is independent of the flow rate of the driven liquid, as predicted by the theory. The core/shell diameters and the size distribution of the generated compound microparticles can be modulated by controlling the flow rates fed to the emitters.
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Simulation of two-dimensional adjustable liquid gradient refractive index (L-GRIN) microlens
NASA Astrophysics Data System (ADS)
Le, Zichun; Wu, Xiang; Sun, Yunli; Du, Ying
2017-07-01
In this paper, a two-dimensional liquid gradient refractive index (L-GRIN) microlens is designed which can be used in adjusting focusing direction and focal spot of light beam. Finite element method (FEM) is used to simulate the convection diffusion process happening in core inlet flow and cladding inlet flow. And the ray tracing method shows us the light beam focusing effect including the extrapolation of focal length and output beam spot size. When the flow rates of the core and cladding fluids are held the same between the internal and external, left and right, and upper and lower inlets, the focal length varied from 313 μm to 53.3 μm while the flow rate of liquids ranges from 500 pL/s to 10,000 pL/s. While the core flow rate is bigger than the cladding inlet flow rate, the light beam will focus on a light spot with a tunable size. By adjusting the ratio of cladding inlet flow rate including Qright/Qleft and Qup/Qdown, we get the adjustable two-dimensional focus direction rather than the one-dimensional focusing. In summary, by adjusting the flow rate of core inlet and cladding inlet, the focal length, output beam spot and focusing direction of the input light beam can be manipulated. We suppose this kind of flexible microlens can be used in integrated optics and lab-on-a-chip system.
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NASA Astrophysics Data System (ADS)
Li, David S.; Yoon, Soon Joon; Matula, Thomas J.; O'Donnell, Matthew; Pozzo, Lilo D.
2017-03-01
A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption 1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.
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NASA Astrophysics Data System (ADS)
Grotberg, James
2005-11-01
This brief overview of our groups activities includes liquid plug propagation in single and bifurcating tubes, a subject which pertains to surfactant delivery, liquid ventilation, pulmonary edema, and drowning. As the plug propagates, a variety of flow patterns may emerge depending on the parameters. It splits unevenly at airway bifurcations and can rupture, which reopens the airway to gas flow. Both propagation and rupture may damage the underlying airway wall cells. Another topic is surfactant dynamics and flow in a model of an oscillating alveolus. The analysis shows a nontrivial cycle-averaged surfactant concentration gradient along the interface that generates steady streaming. The steady streaming patterns particularly depend on the ratio of inspiration to expiration time periods and the sorption parameter. Vortices, single and multiple, may be achieved, as well as a saddle point configuration. Potential applications are pulmonary drug administration, cell-cell signaling pathways, and gene therapy. Finally, capillary instabilities which cause airway closure, and strategies for stabilization, will be presented. This involves the core-annular flow of a liquid-lined tube, where the core (air) is forced to oscillate axially. The stabilization mechanism is similar to that of a reversing butter knife, where the core shear wipes the growing liquid bulge, from the Rayleigh instability, back on to the tube wall during the main tidal volume stroke, but allows it to grow back as the stroke and shear turn around.
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Constraints on Mercury's Core-Mantle Boundary Region
NASA Astrophysics Data System (ADS)
Hauck, S. A., II; Chabot, N. L.; Sun, P.; Jing, Z.; Johnson, C. L.; Margot, J. L.; Padovan, S.; Peale, S. J.; Phillips, R. J.; Solomon, S. C.
2014-12-01
Understanding the boundary between a planet's metallic core and silicate mantle is important for constraining processes that dominate on either side of this boundary. Geophysical measurements of the planet Mercury by the MESSENGER spacecraft have provided evidence of a core larger than earlier, less-constrained estimates. Further, these results, taken in concert with measurements of the elemental composition of the surface by MESSENGER, have led to the suggestion that the uppermost layer of the outer core may be highly enriched in sulfur, and the top of the core may consist of a solid sulfide layer. The low iron and relatively large sulfur contents of the surface indicate highly reducing conditions during planet formation, placing constraints on the potential composition of Mercury's core. Recent metal-silicate partitioning experiments have developed new limits on the amount of sulfur and silicon that may partition into the core as a function of sulfur abundance at the surface. Models for the planet's internal structure constrained by the current best estimates of the bulk density, normalized polar moment of inertia, and fraction of the polar moment of inertia of the solid layer that extends from the surface to the top of the liquid outer core provide an important view of the layering and bulk composition of Mercury. By combining the results of these internal structure models with the experimental relationship between core and mantle composition we place new limits on core composition and structure. Further, imposing measured compositional constraints on the miscibility of iron-sulfur-silicon alloys yields important limits on the presence or absence of an immiscible sulfur-rich liquid layer or a solid sulfide layer at the top of the core.
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Differentiated planetesimal impacts into a terrestrial magma ocean: Fate of the iron core
NASA Astrophysics Data System (ADS)
Kendall, Jordan D.; Melosh, H. J.
2016-08-01
The abundance of moderately siderophile elements (;iron-loving;; e.g. Co, Ni) in the Earth's mantle is 10 to 100 times larger than predicted by chemical equilibrium between silicate melt and iron at low pressure, but it does match expectation for equilibrium at high pressure and temperature. Recent studies of differentiated planetesimal impacts assume that planetesimal cores survive the impact intact as concentrated masses that passively settle from a zero initial velocity and undergo turbulent entrainment in a global magma ocean; under these conditions, cores greater than 10 km in diameter do not fully mix without a sufficiently deep magma ocean. We have performed hydrocode simulations that revise this assumption and yield a clearer picture of the impact process for differentiated planetesimals possessing iron cores with radius = 100 km that impact into magma oceans. The impact process strips away the silicate mantle of the planetesimal and then stretches the iron core, dispersing the liquid iron into a much larger volume of the underlying liquid silicate mantle. Lagrangian tracer particles track the initially intact iron core as the impact stretches and disperses the core. The final displacement distance of initially closest tracer pairs gives a metric of core stretching. The statistics of stretching imply mixing that separates the iron core into sheets, ligaments, and smaller fragments, on a scale of 10 km or less. The impact dispersed core fragments undergo further mixing through turbulent entrainment as the molten iron fragments rain through the magma ocean and settle deeper into the planet. Our results thus support the idea that iron in the cores of even large differentiated planetesimals can chemically equilibrate deep in a terrestrial magma ocean.
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NASA Astrophysics Data System (ADS)
Reitberger, Thomas; Hoffmann, Gerd-Albert; Wolfer, Tim; Overmeyer, Ludger; Franke, Joerg
2016-09-01
The optical data transfer is considered as the future of signal transfer due to its various advantages compared to conventional copper-based technologies. The Aerosol Jet Printing (AJP) technology offers the opportunity to print materials with high viscosities, such as liquid transparent polymer adhesives (epoxy resins), on almost any possible substrate material and even in third dimension. This paper introduces a new flexible and comparatively cost-effective way of generating polymer optical waveguides through AJP. Furthermore, the conditioning of the substrate material and the printing process of planar waveguides are presented. In the first step, two lines with hydrophobic behavior are applied on foil material (PMMA, PVC, PI) by using a flexographic printing machine. These silicone based patterns containing functional polymer form barriers for the core material due to their low surface energy after curing. In the second step, the core material (liquid polymer, varnish) is printed between the barrier lines. Because of the hydrophobic behavior of the lines, the contact angle between the substrate surface and the liquid core material is increased which yields to higher aspect ratio. The distance between the barrier lines is at least 100 μm, which defines the width of the waveguide. The minimum height of the core shall be 50 μm. After UV-curing of the core polymer, the cladding material is printed on the top. This is also applied by using the AJP technology. Various tests were performed to achieve the optimal surface properties for adequate adhesion and machine process parameters.
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NASA Technical Reports Server (NTRS)
Stevenson, D. J.
1981-01-01
Combined inferences from seismology, high-pressure experiment and theory, geomagnetism, fluid dynamics, and current views of terrestrial planetary evolution lead to models of the earth's core with five basic properties. These are that core formation was contemporaneous with earth accretion; the core is not in chemical equilibrium with the mantle; the outer core is a fluid iron alloy containing significant quantities of lighter elements and is probably almost adiabatic and compositionally uniform; the more iron-rich inner solid core is a consequence of partial freezing of the outer core, and the energy release from this process sustains the earth's magnetic field; and the thermodynamic properties of the core are well constrained by the application of liquid-state theory to seismic and labroatory data.
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The curious case of Mercury's internal structure
NASA Astrophysics Data System (ADS)
Hauck, Steven A.; Margot, Jean-Luc; Solomon, Sean C.; Phillips, Roger J.; Johnson, Catherine L.; Lemoine, Frank G.; Mazarico, Erwan; McCoy, Timothy J.; Padovan, Sebastiano; Peale, Stanton J.; Perry, Mark E.; Smith, David E.; Zuber, Maria T.
2013-06-01
The recent determination of the gravity field of Mercury and new Earth-based radar observations of the planet's spin state afford the opportunity to explore Mercury's internal structure. These observations provide estimates of two measures of the radial mass distribution of Mercury: the normalized polar moment of inertia and the fractional polar moment of inertia of the solid portion of the planet overlying the liquid core. Employing Monte Carlo techniques, we calculate several million models of the radial density structure of Mercury consistent with its radius and bulk density and constrained by these moment of inertia parameters. We estimate that the top of the liquid core is at a radius of 2020 ± 30 km, the mean density above this boundary is 3380 ± 200 kg m-3, and the density below the boundary is 6980 ± 280 kg m-3. We find that these internal structure parameters are robust across a broad range of compositional models for the core and planet as a whole. Geochemical observations of Mercury's surface by MESSENGER indicate a chemically reducing environment that would favor the partitioning of silicon or both silicon and sulfur into the metallic core during core-mantle differentiation. For a core composed of Fe-S-Si materials, the thermodynamic properties at elevated pressures and temperatures suggest that an FeS-rich layer could form at the top of the core and that a portion of it may be presently solid.
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NASA Astrophysics Data System (ADS)
Han, Yun; Oo, Maung Khaing; Zhu, Yinian; Sukhishvili, Svetlana; Xiao, Limin; Demokan, M. Süleyman; Jin, Wei; Du, Henry
2007-09-01
We have explored the use of index-guiding liquid-core photonic crystal fiber (LC-PCF) as a platform for sensing and measurements of analyte solutions of minute volume by normal and surface-enhanced Raman scattering (SERS). The index-guiding LC-PCF was fabricated by selectively sealing via fusion splicing the cladding air channels of a hollow-core PCF (HC-PCF) while leaving the center core open at both ends of the fiber. The center core of the resultant fiber was subsequently filled with water-ethanol solution mixtures at various ethanol concentrations for normal Raman scattering measurements and with water-thiocynate solutions containing Ag nanoparticle aggregates for SERS detection of thiocynate at trace concentrations. The light-guiding nature in the solution phase inside the LC-PCF allows direct and strong light-field overlap with the solution phase over the entire length of the PCF (~30 cm). This detection scheme also dramatically reduces the contribution of silica to Raman spectral background, compared with the solid-core counterpart, thus its potential interference in spectral analysis. These features attribute to ready normal Raman measurements of water, ethanol, and water (99 vol.%)-ethanol (1 vol.%) solutions as well as sensitive and reproducible SERS detection of ~10 ppb thiocynate in water, all at a volume of ~0.1 μL.
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To development of analytical theory of rotational motion of the Moon
NASA Astrophysics Data System (ADS)
Barkin, Yu. V.; Ferrandiz, J. M.; Navarro, J. F.
2009-04-01
Resume. In the work the analytical theory of forced librations of the Moon considered as a celestial body with a liquid core and rigid non-spherical mantle is developed. For the basic variables: Andoyer, Poincare and Eulerian angles, and also for various dynamic characteristics of the Moon the tables for amplitudes, periods and phases of perturbations of the first order have been constructed. Resonant periods of free librations have been estimated. The influence of a liquid core results in decreasing of the period of free librations in longitude approximately on 0.316 day, and in change of the period of free pole wobble of the Moon on 25.8 days. In the first approximation the liquid core does not render influence on the value of Cassini's inclination and on the period of precession of the angular momentum vector. However it causes an additional "quasi-diurnal" librations with period about 27.165 days. In comparison with model of rigid non-spherical of the Moon the presence of a liquid core should result in increase of amplitudes of the Moon librations in longitude on 0.06 %. 1 Development of analytical theory of rotational motion of the Moon with liquid core and rigid mantle. The work has been realized in following stages. 1. Canonical equations of rotation of the Moon with liquid core and elastic mantle in Andoyer and Poincare variables have been constructed. Developments of second harmonic of force function of the Moon in pointed variables have been obtained for accurate trigonometric presentation of perturbations of the Moon orbital motion. 2. Two approaches (two methods) of construction of analytical theory have been developed. These approaches use different principles for eliminating of singularities for axial rotation of the Moon. One is based on direct application of Andoyer variables by changing of notations of moments of inertia [1]. Second is based on application of Poincare elements. For comparison both approaches are developed. 3. The main equation for determination of Cassini's inclination and its solution has been obtained in the case of accurate orbit of the Moon. An dynamical explanation of Cassini's laws has been done for model of the Moon with liquid core [2]. 4. Compact formulae for perturbations of the first (and second) order have been constructed for general used variables and for different kinematical and dynamical characteristics of the Moon (23 variables and characteristics: Andoyer-Poincare variables, classical variables, components of angular velocity and angular momentums of the Moon and its core). 5. Analytical formulae for 4 periods of free librations of the Moon have been constructed: for librations in longitude, in pole wobble, for free precession, and "quasi-diurnal" librations, caused by the liquid core. 6. The dynamical effects in the Moon rotation, caused by secular orbital perturbations of the Earth and Sun, have been studied. 2 Structure perturbations of the first order and their tabulation. For example, perturbations (periodic and of mixed type) in inclination ?and in node h of angular momentum of the Moon are determined by formulae: ? = ?0 + ???(1) cosθv, h = ? + ¥?¥h?(1) sinθ?. Here ?0 = 1033â²50" is the Cassini's inclination of the Moon; ??(1), h?(1)are constant coefficients; θv = v1lM + v2lS + v3F + v4D, ? = (v1,v2,v3,v4)Tare combinations of known classical arguments of the Moon orbital theory; v1,v2,v3 and v4 are integer. 3 Influence of the liquid core and its ellipticity É on amplitudes of the Moon forced and free librations. An influence of the liquid core and its ellipticity is determined by positive correction to amplitudes of librations for model of the rigid Moon. If the amplitudes of librations of rigid Moon we note as 1, so the corresponding amplitudes of librations of the Moon with the liquid core will be characterized by parameter 1 + L, where correction for liquid core is determined by formula L = Cc(1- É2)C ? CcC = 0.5996 × 10-3, where Cand Ccis the polar moments of inertia of the Moon and its core;É = (a2 - b2) (a2 + b2)? (a - b)a is an ellipticity of equatorial ellipse of core cavity with semi-axes a and b. So all amplitudes of librations in longitude due to the liquid core are increased on 0.06%. A small effect of ellipticity has more smaller order. Here as example we present formula for perturbations of the first order of the Moon in longitude: (1) 21-+-L λ = 6n0 I C22Ã- D (1) (? )- D(-1) (? ) Ã- (- 1)?5-?1.?2.?3+2.?4.?5--0----?1.?2.?3-2.?4.?25-0-sin(v1lM + v2lS + v3F + v4D ) ¥?¥>0 ?5 (v1nM + v2nS + v3nF + v4nD) I = C(mr2) is the dimensionless moment of inertia of the Moon (m and rare it's the mass and mean radius). Kinoshita's inclination functions D?1.?2.?3.?4.?5(±1)(? 0) are determined by known formulae through the value of Cassini's angle? = 1033â²50". v1nM + v2nS + v3nF + v4nD = Ëθv1,v2,v3,v4 are derivatives with respect to the time of corresponding linear combinations of classical arguments of lunar orbit theory; nM,nS,nF and nD are velocities of changes of these arguments; C22 is the selenopotential coefficient; n02 = fmâa3, a is an unperturbed value of semi-axis major of lunar orbit, fis a gravitational constant. The perturbations of the first order for others variables and considered dynamical characteristics have the structure similar to the formula for Ëλ(1). In given table 1 we present amplitudes of forced librations in longitude of intermediate Andoyer plane λ?1,?2,?3,?4 (in arc seconds) and perturbations of angular velocity of the Moon axial rotation ??1,?2,?3,?4 (in units10-4nF). T?1,?2,?3,?4are periods of corresponding perturbations. Table 1. Main perturbations in the Moon librations in longitude. ?1 ?2 ?3 ?4 T?1,?2,?3,?4 λ?1,?2,?3,?4 0 1 0 0 365.26 81"02 1 0 0 0 27.555 -15"65 1 -1 0 -1 -3232.9 9"85 2 0 0 -2 205.89 9"69 1 0 0 -2 31.81 4"15 1 0 0 -1 411.78 -2"98 2 0 -2 0 -1095.2 -1"86 2 -1 0 -2 471.89 0"74 0 0 0 2 14.77 -0"61 The results of tabulations of amplitudes of perturbations in the Moon rotation give good agreement with earlier constructed theories for its rigid model. Barkin's work partially was financially accepted by Spanish grants, Japanese-Russian grant N-07-02-91212 and by RFBR grant N 08-02-00367. References [1] Barkin, Yu. (1987) An Analytical Theory of the Lunar Rotational Motion. In: Figure and Dynamics of the Earth, Moon and Planets/ Proceedings of the Int. Symp. (Prague, Czechoslovakia, Sept. 15-20, 1986)/ Monogr. Ser. of UGTK, Prague. pp. 657-677. [2] Ferrandiz, J., Barkin, Yu. (2003) New approach to development of Moon rotation theory. Procced. of Inter. Conf. "Astrometry, Geodynamics and Solar System Dynamics". Journees 2003 (Sept. 22-25, 2003, St. Peters., Russia). IPA RAS, 199-200.
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Vinci, Giuliana; Antonelli, Marta L; Preti, Raffaella
2013-02-01
Liquid-liquid microextraction coupled to LC with fluorescence detection for the determination of Environmental Protection Agency's 16 priority pollutant polycyclic aromatic hydrocarbons in rainwater has been developed. The optimization of the extraction method has involved several parameters, including the comparison between an ultrasonic bath and a magnetic stirrer as extractant apparatus, the choice of the extractant solvent, and the optimization of the extraction time. Liquid-liquid microextraction gave good results in terms of recoveries (from 73.6 to 102.8% in rainwater) and repeatability, with a very simple procedure and low solvent consumption. The reported chromatographic method uses a Core-Shell technology column, with particle size <3 μm instead of classical 5-μm particles column. The resulting backpressure was below 300 bar, allowing the use of a conventional HPLC system rather than the more expensive ultrahigh performance LC (UHPLC). An average decrease of 59% in run time and 75% in eluent consumption has been obtained, compared to classical HPLC methods, keeping good separation, sensitivity, and repeatability. The proposed conditions were successfully applied to the determinations of polycyclic aromatic hydrocarbons in genuine rainwater samples. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Large core plastic planar optical splitter fabricated by 3D printing technology
NASA Astrophysics Data System (ADS)
Prajzler, Václav; Kulha, Pavel; Knietel, Marian; Enser, Herbert
2017-10-01
We report on the design, fabrication and optical properties of large core multimode optical polymer splitter fabricated using fill up core polymer in substrate that was made by 3D printing technology. The splitter was designed by the beam propagation method intended for assembling large core waveguide fibers with 735 μm diameter. Waveguide core layers were made of optically clear liquid adhesive, and Veroclear polymer was used as substrate and cover layers. Measurement of optical losses proved that the insertion optical loss was lower than 6.8 dB in the visible spectrum.
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NASA Astrophysics Data System (ADS)
Brown, W. L.; Toplis, M. J.
2003-04-01
Due to slow NaSi-CaAl exchange in plagioclase, the proportion of the anorthite component (An) may be considered essentially a primary feature in magmatic bodies such as small layered intrusions. Thus, An provides a potential window into the evolution of such magmatic systems on various length scales. In order to assess the utility of this approach, 13 thin sections covering the principal zones and sub-zones of the Layered Series of the Skaergaard intrusion, East Greenland, were studied. In each thin section 90 to 150 analyses of plagioclase were made using an electron microprobe. Analyses were made in grain centres and at grain edges, particular attention being paid to plagioclase-plagioclase contacts. The cores of large and moderately sized crystals show narrow compositional ranges, 90% of analyses lying within 3 mol% of the mean. In accordance with previous studies, we find that mean core compositions vary continuously with stratigraphic height, from ˜An70 at the lowest levels, to ˜An30 at the top of Upper Zone (UZ). Rim compositions of touching plagioclase also show strong maxima in their mode, but the variation of this composition with stratigraphic height is distinctly different from that of crystal cores. In the Lower Zone (LZ) and lower Middle Zone (MZ), the most abundant rim compositions are systematically An50± 1, core and rim compositions converging in the lower MZ. In the upper MZ to UZ, rim compositions are very similar to corresponding cores, but locally may be more evolved, particularly when plagioclase is intergrown with quartz. The systematic decrease of An as a function of stratigraphic height is strong evidence in favour of fractional crystallization of the main liquid. However, the fact that plagioclase zoning does not extend to nearly pure albite in the vast majority of rocks implies mobility of intercumulus liquid. If compaction (expulsion) were the mechanism responsible for this, it would be difficult to explain the remarkably constant cut-off in rim compositions at An50 in the LZ and lower MZ. On the other hand, this cut-off corresponds to the An content at magnetite saturation, which leads us to propose that the observed features are the result of a density inversion in the liquid following oxide saturation. This density inversion causes the intercumulus liquid to become gravitationally unstable relative to the overlying main liquid leading to compositional convection in the upper LZ and MZ, a hypothesis consistent with the adcumulus texture of those rocks.
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Density Measurement of Liquid FeS Under High Pressure and High Temperature
NASA Astrophysics Data System (ADS)
Yu, T.; Young, C.; Chen, J.; Baldwin, K.
2005-05-01
Sulfur is considered one of the possible light elements in the core which might be responsible for the density deficit. We studied the liquid state of sulfur in iron due to sulfur¡¦s lack of amount in the mantle; easiness to alloy with iron; and the predicted 5% ~ 10% amount of this light element in the core (Ahrens, 1979; Sherman, 1997). Restricted by the modern development of the multianvil high pressure experimental equipments, the experiments are limited at a lower pressure range (<30GPa) comparing with the outer core pressure condition. Therefore, extrapolation of data derived at low pressure range to the condition of the outer core (130-330GPa) has to be applied and may produce results which are way far from the true numbers. However, at the point while the techniques are limited, studying the physical properties of the molten FeS at relatively low pressure still provides us a better picture of the physical behaviors of the liquid outer core comparing with data derived from solid state FeS experiments. The lack of melt density data at low pressure provides another motivation for us to study the physical properties of melt. The radiography (shadowgraphy) system on Beam Line X17B2, NSLS at the Brookhaven National Laboratory is an add-on system attached to the in situ x-ray beam line setup. It includes a YAG fluorescent screen, an optical mirror, focusing-magnification lenses, and a CCD camera and/or a video camera. Before the melting temperature, the radiograph system yields a maximum 1% difference in density comparing with the data collected by the traditional x-ray diffraction method. We have successfully examined liquid FeS samples by applying this technique at the NSLS. With a sapphire (Al2O3) sphere surrounded by FeS powder. The image of the sphere was clearly shown due to the absorption coefficient difference between these two materials. The density fitting method developed by our group has produced convincing data. The preliminary results of the density measurements of molten FeS show that the derived liquid density variation for the same sample remains under 1%. This study has collected in situ high pressure and high temperature x-ray diffraction data of the FeS sample up to 4GPa and 1400°C. Combined with the derived density data, the equation of state of the liquid FeS can be constructed.
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A dual-parameter tilted fiber Bragg grating-based sensor for liquid level and temperature monitoring
NASA Astrophysics Data System (ADS)
Osuch, Tomasz; Jurek, Tomasz; Markowski, Konrad; Jedrzejewski, Kazimierz
2016-09-01
In this paper, the concept and experimental characterization of tilted fiber Bragg grating (TFBG) based sensor for temperature and liquid level measurement are presented. It is shown that, when liquid level increases the peak amplitudes of cladding modes linearly decreases (in dB). In turn, changes in temperature causes a shift of the TFBG transmission spectrum, which can be accurately measured by monitoring the Bragg wavelength corresponding to the liquid level independent core mode. The main advantages of proposed sensor are simple design as well as linear responses to liquid level and temperature.
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Armored spring-core superconducting cable and method of construction
McIntyre, Peter M.; Soika, Rainer H.
2002-01-01
An armored spring-core superconducting cable (12) is provided. The armored spring-core superconducting cable (12) may include a spring-core (20), at least one superconducting strand (24) wound onto the spring-core (20), and an armored shell (22) that encases the superconducting strands (24). The spring-core (20) is generally a perforated tube that allows purge gases and cryogenic liquids to be circulated through the armored superconducting cable (12), as well as managing the internal stresses within the armored spring-core superconducting cable (12). The armored shell (22) manages the external stresses of the armored spring-core superconducting cable (12) to protect the fragile superconducting strands (24). The armored spring-core superconducting cable (12) may also include a conductive jacket (34) formed outwardly of the armored shell (22).
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Pelevina, I I; Aleshchenko, A V; Antoshchina, M M; Kudriashova, O M; Nikonova, M F; Riabchenko, N I; Serebrianyĭ, A M; Iarilin, A A
2013-01-01
Expression of activation (CD69) and proliferation (Ki67) markers, their connection with each other, with the oxidative status (reactive oxygen species--ROS) and with radiosensitivity (determined by micronucleus test) have been studied on stimulated blood lymphocytes from Moscow inhabitants. It was shown that the content of T-lymphocytes with the expressed CD69 and the content of T-lymphocytes with the expressed Ki67 markers correlate (r = 0.571; p = 0.0004). We can suppose that expression of the CD69 marker (24 h after PHA stimulation) is needed for the cell cycle progression, but it is not enough for the high expression of Ki67 markers 48 h after stimulation (DNA synthesis phase). It was discovered that T-lymphocytes with the CD69 marker or T-lymphocytes with the Ki67 marker are connected by the negative correlation with the frequency of irradiated cell with micronucleus (MN) r = -0.487; p = 0.010; r = -0.440; p = 0.008, respectively. So we can suppose that lymphocyte radiosensitivity decreased with the increase of expression activation and proliferation markers. It was shown that radiosensitivity determined by MN test is not connected with the oxidative status determined by the reactive oxygen species content including superoxide anion radicals. It is possible to explain by the fact that the ROS concentration has been determined in non-stimulated lymphocytes, but frequencies of cells with MN - in the stimulated cells 48 h after stimulation. Using separate analysis of individual differences by the studied parameters that were determined in the same people, it was shown that individual differences are high enough in the same cases. For example, the radiosensitivity when cells were irradiated 48 h after stimulation, ROS concentration, cell content with activation and proliferation markers. In conclusion, we can say that we failed to find important correlation between the parameters studied. However, the presence of individual differences in the marker expression, the frequency of MN cells, the oxidative status in the usual inhabitants, typical donors in Moscow, is very important.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg; Zhu Congju; Wong Yinling
Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival,more » {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G{sub 2}/M arrest, and DNA DSBs, compared with nonstem glioma cells. Gefitinib differentially enhances radiosensitivity of stem-like gliomaspheres by reducing EGFR-Akt activation and DNA-PKcs expression, accompanied by enhanced irradiation-induced DNA DSBs and inhibition of DSB repair.« less
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Kang, Khong Bee; Zhu, Congju; Wong, Yin Ling; Gao, Qiuhan; Ty, Albert; Wong, Meng Cheong
2012-05-01
We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H(2)AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H(2)AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G(2)/M arrest and increased γ-H(2)AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H(2)AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G(2)/M arrest, and DNA DSBs, compared with nonstem glioma cells. Gefitinib differentially enhances radiosensitivity of stem-like gliomaspheres by reducing EGFR-Akt activation and DNA-PKcs expression, accompanied by enhanced irradiation-induced DNA DSBs and inhibition of DSB repair. Copyright © 2012 Elsevier Inc. All rights reserved.
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Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer cells.
Sørensen, Brita Singers; Busk, Morten; Olthof, Nadine; Speel, Ernst-Jan; Horsman, Michael R; Alsner, Jan; Overgaard, Jens
2013-09-01
HPV associated Head and Neck Squamous Cell Carcinoma (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. Previous data from the randomized DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic modifications by Nimorazole during radiotherapy, whereas a significant benefit was observed in the HPV negative tumors. However, more studies have demonstrated equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors. The aim of the present study was to determine radiosensitivity, the impact of hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines. The used cell lines were: UDSCC2, UMSCC47 and UPCISCC90 (HPV positive) and FaDuDD, UTSCC33 and UTSCC5 (HPV negative). Cells were cultured under normoxic or hypoxic conditions, and gene expression levels of previously established hypoxia induced genes were assessed by qPCR. Cells were irradiated with various doses under normoxia, hypoxia or hypoxia +1mM Nimorazole, and the clonogenic survival was determined. The HPV positive and HPV negative cell lines exhibited similar patterns of upregulation of hypoxia induced genes in response to hypoxia. The HPV positive cell lines were up to 2.4 times more radiation sensitive than HPV negative cell lines. However, all HPV positive cells displayed the same response to hypoxia in radiosensitivity, with an OER in the range 2.3-2.9, and a sensitizer effect of Nimorazole of 1.13-1.29, similar to HPV negative cells. Although HPV positive cells had a markedly higher radiosensitivity compared to HPV negative cells, they displayed the same relative radioresistance under hypoxia and the same relative sensitizer effect of Nimorazole. The clinical observation that HPV positive patients do not seem to benefit from Nimorazole treatment is not due to inherent differences in hypoxia sensitivity or response to Nimorazole, but can be accounted for by the overall higher radiosensitivity of HPV positive cells. Copyright © 2013. Published by Elsevier Ireland Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ohri, Nitin; Dicker, Adam P.; Lawrence, Yaacov Richard, E-mail: yaacovla@gmail.com
2012-05-01
Purpose: Hypofractionated radiotherapy (hRT) is being explored for a number of malignancies. The potential benefit of giving concurrent chemotherapy with hRT is not known. We sought to predict the effects of combined modality treatments by using mathematical models derived from laboratory data. Methods and Materials: Data from 26 published clonogenic survival assays for cancer cell lines with and without the use of radiosensitizing chemotherapy were collected. The first three data points of the RT arm of each assay were used to derive parameters for the linear quadratic (LQ) model, the multitarget (MT) model, and the generalized linear quadratic (gLQ) model.more » For each assay and model, the difference between the predicted and observed surviving fractions at the highest tested RT dose was calculated. The gLQ model was fitted to all the data from each RT cell survival assay, and the biologically equivalent doses in 2-Gy fractions (EQD2s) of clinically relevant hRT regimens were calculated. The increase in cell kill conferred by the addition of chemotherapy was used to estimate the EQD2 of hRT along with a radiosensitizing agent. For comparison, this was repeated using conventionally fractionated RT regimens. Results: At a mean RT dose of 8.0 Gy, the average errors for the LQ, MT, and gLQ models were 1.63, 0.83, and 0.56 log units, respectively, favoring the gLQ model (p < 0.05). Radiosensitizing chemotherapy increased the EQD2 of hRT schedules by an average of 28% to 82%, depending on disease site. This increase was similar to the gains predicted for the addition of chemotherapy to conventionally fractionated RT. Conclusions: Based on published in vitro assays, the gLQ equation is superior to the LQ and MT models in predicting cell kill at high doses of RT. Modeling exercises demonstrate that significant increases in biologically equivalent dose may be achieved with the addition of radiosensitizing agents to hRT. Clinical study of this approach is warranted.« less