878 research outputs found

    Differential Games with Ergodic Payoff

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    Effect of the C/N ratio modification on the corrosion behavior and performance of carbonitride coatings prepared by cathodic arc deposition

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    This study focuses on investigating carbonitride coatings, specifically CNTi-(Zr, ZrNb, and ZrSi), as promising candidates for enhancing the durability and efficiency of Ti6Al4V materials used in nuclear fusion technology. X-ray diffraction analysis identified distinct phases, including TiN, ZrN, ZrC, and TiC. The corrosion studies showed complete degradation of the TiN, ZrC, and ZrN phases in the TiZrCN coating after tests, while the TiC phase exhibited relative stability. The surface morphologies and elemental mapping analysis demonstrated the loss of homogeneity in element distribution after corrosion process. The addition of Si and Nb elements into TiZrCN significantly influenced the coatings' corrosion behavior, with breakaway corrosion observed in CNTi- (Zr and ZrSi) coatings and localized corrosion in CNTi-(ZrNb) coatings. Notably, the CNTi-(ZrSi) coating formed an oxide phase in the presence of NaCl, whereas the CNTi-(ZrNb) coating exhibited continuous resistance and a low corrosion rate. Irradiation was carried out for the generation of active isotopes, showing that no radioactive isotopes were formed in any of the investigated samples

    Remote Pulsed Laser Raman Spectroscopy System for Detecting Qater, Ice, and Hydrous Minerals

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    For exploration of planetary surfaces, detection of water and ice is of great interest in supporting existence of life on other planets. Therefore, a remote Raman spectroscopy system was demonstrated at NASA Langley Research Center in collaboration with University of Hawaii for detecting ice-water and hydrous minerals on planetary surfaces. In this study, a 532 nm pulsed laser is utilized as an excitation source to allow detection in high background radiation conditions. The Raman scattered signal is collected by a 4-inch telescope positioned in front of a spectrograph. The Raman spectrum is analyzed using a spectrograph equipped with a holographic super notch filter to eliminate Rayleigh scattering, and a holographic transmission grating that simultaneously disperses two spectral tracks onto the detector for higher spectral range. To view the spectrum, the spectrograph is coupled to an intensified charge-coupled device (ICCD), which allows detection of very weak Stokes line. The ICCD is operated in gated mode to further suppress effects from background radiation and long-lived fluorescence. The sample is placed at 5.6 m from the telescope, and the laser is mounted on the telescope in a coaxial geometry to achieve maximum performance. The system was calibrated using the spectral lines of a Neon lamp source. To evaluate the system, Raman standard samples such as calcite, naphthalene, acetone, and isopropyl alcohol were analyzed. The Raman evaluation technique was used to analyze water, ice and other hydrous minerals and results from these species are presented

    Design, synthesis, and DNA interaction studies of furo-imidazo[3.3.3] propellane derivatives : Potential anticancer agents

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    A large number of natural products containing the propellane scaffold have been reported to exhibit cytotoxicity against several cancers; however, their mechanism of action is still unknown. Anticancer drugs targeting DNA are mainly composed of small planar molecule/s that can interact with the DNA helix, causing DNA malfunction and cell death. The aim of this study was to design and synthesize propellane derivatives that can act as DNA intercalators and/or groove binders. The unique structure of the propellane derivatives and their ability to display planar ligands with numerous possible geometries, renders them potential starting points to design new drugs targeting DNA in cancer cells. New substituted furo-imidazo[3.3.3]propellanes were synthesized via the reaction of substituted alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydr- 1H-2-ylidene) propanedinitrile in tetrahydrofuran at room temperature. The structures of the products were confirmed by a combination of elemental analysis, NMR, ESI-MS, IR and single crystal X-ray analysis. Interestingly, 5c, 5d and 5f showed an ability to interact with Calf Thymus DNA (CT-DNA). Their DNA-binding mode was investigated using a combination of absorption spectroscopy, DNA melting, viscosity, CD spectroscopy measurements, as well as competitive binding studies with several dyes. Their cytotoxicity was evaluated against the NCI-60 panel of cancer cell lines. 5c, 5d and 5f exhibited similar anti-proliferative activity against the A549 non-small cell lung cancer (NSCLC) cell line. Further mechanistic studies revealed their ability to induce DNA damage in the A549 cell line, as well as apoptosis, evidenced by elevated Annexin V expression, enhanced caspase 3/7 activation and PARP cleavage. In this study, we present the potential for designing novel propellanes to provoke cytotoxic activity, likely through DNA binding-induced DNA damage and apoptosis.Peer reviewe

    Design, synthesis and biological evaluation of fused naphthofuro[3,2-c]quinoline-6,7,12-triones and pyrano[3,2-c]quinoline-6,7,8,13-tetraones derivatives as ERK inhibitors with efficacy in BRAF-mutant melanoma

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    Approximately 60% of human cancers exhibit enhanced activity of ERK1 and ERK2, reflecting their multiple roles in tumor initiation and progression. Acquired drug resistance, especially mechanisms associated with the reactivation of the MAPK (RAF/MEK/ERK) pathway represent a major challenge to current treatments of melanoma and several other cancers. Recently, targeting ERK has evolved as a potentially attractive strategy to overcome this resistance. Herein, we report the design and synthesis of novel series of fused naphthofuro[3,2-c] quinoline-6,7,12-triones 3a-f and pyrano[3,2-c]quinoline-6,7,8,13-tetraones 5a,b and 6, as potential ERK inhibitors. New inhibitors were synthesized and identified by different spectroscopic techniques and X-ray crystallography. They were evaluated for their ability to inhibit ERK1/2 in an in vitro radioactive kinase assay. 3b and 6 inhibited ERK1 with IC50s of 0.5 and 0.19 mu M, and inhibited ERK2 with IC50s of 0.6 and 0.16 mu M respectively. Kinetic mechanism studies revealed that the inhibitors are ATP-competitive inhibitors where 6 inhibited ERK2 with a K-i of 0.09 mu M. Six of the new inhibitors were tested for their in vitro anticancer activity against the NCI-60 panel of tumor cell lines. Compound 3b and 6 were the most potent against most of the human tumor cell lines tested. Moreover, 3b and 6 inhibited the proliferation of the BRAF mutant A375 melanoma cells with IC50s of 3.7 and 0.13 mu M, respectively. In addition, they suppressed anchorage-dependent colony formation. Treatment of the A375 cell line with 3b and 6 inhibited the phosphorylation of ERK substrates p-90RSK and ELK-1 and induced apoptosis in a dose dependent manner. Finally, a molecular docking study showed the potential binding mode of 3b and 6 within the ATP catalytic binding site of ERK2.Peer reviewe

    Hyper-arid tall shrub species have differing long-term responses to browsing management

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    © 2019, © 2019 Taylor & Francis Group, LLC. Hyper-arid rangeland vegetation is typically dominated by large woody species which are often overlooked in herbivory studies. Long-term responses of tall shrub populations to herbivory change are poorly understood in the Arabian Peninsula. Population and size of 1559 individuals from four shrub species were assessed over an 11-year period under two herbivory regimes, one in which domestic livestock (camels) were replaced by semi-wild ungulates (Oryx and gazelles) before, and the other during, the study period. Each shrub species exhibited a different response to the change in herbivory. Populations of Calotropis procera decreased dramatically. Populations of both Calligonum polygonoides and Lycium shawii increased through sexual reproduction, but the spatial distribution of recruits indicated different modes of seed dispersal. Average lifespans were estimated at 22 and 20years respectively. The persistence strategy of Leptadenia pyrotechnica was similar to tree species of this habitat in that vegetative regrowth was prioritized over recruitment, and average lifespan was estimated at 95years. Shrub responses to changes in ungulate management are therefore species-specific. The response of individual plant size was faster than the response of population size, which was limited by slow sexual recruitment (L. pyrotechnica) or localized seed dispersal (C. polygonoides)

    Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

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    BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

    Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

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    We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings
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