247 research outputs found

    Gas Phase Diagnostics of CVD Diamond Growth From Chloromethane and Chloroform

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    Low energy electron impact ionization (LEEII) time of flight mass spectrometry (TOFMS) has been used to interrogate gases sampled through an orifice from a diamond growth surface. Methane, chloromethane and chloroform precursor gases were examined to produce electron energy plots of the fragment ions that occur using LEEII. Filament temperature studies were completed covering temperatures from room temperature to over 2000 °C, and the results were compared to the LEEII plots. The monochloromethyl radical has been detected in the experiments using chloroform and the effect of a pretreatment with this radical present has been shown to enhance diamond nucleation. Scanning electron microscopy (SEM) and Raman spectroscopy have been used to confirm diamond growth

    Characterization of blood drawn rapidly for use in blood volume expansion studies: An animal model for simulated weightlessness

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    It was demonstrated that up to 8ml of blood can be drawn from donar rats without significantly increasing volume and stress sensitive hormones, and thus can be used for volume expansion studies. Infusion of whole blood allows more physiological changes that can be seen with volume expansion by saline or other ionic solutions. The infusion of whole blood to induce hypervolemia may provide an improved model to study the fluid balance and control mechanisms operative in weightlessness. Blood samples were drawn as quickly as possible from femoral artery catheters chronically implanted in Sprague Dawley rats and analyzed for hematocrit, plasma sodium, potassium, osmolality, corticosterone, epinepherine, norepinephrine, and vasopressin. The levels were found to be comparable to those of normal rats

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    Melengestrol Acetate at Greater Doses Than Typically Used for Estrous Synchrony in Bovine Females Does Not Mimic Endogenous Progesterone in Regulation of Secretion of Luteinizing Hormone and 17β-Estradiol

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    Our working hypothesis was that doses of melengestrol acetate (MGA) greater than those typically administered in estrous synchrony regimens would regulate secretion of LH and 17β-estradiol (E2) as endogenous progesterone (P4) does during the midluteal phase of the estrous cycle. We also hypothesized that endogenous P4 from the CL would interact with MGA to further decrease the frequency of LH pulses and E2. Cows on Day 5 of their estrous cycle (Day 0 = estrus) were randomly assigned to an untreated control group (CONT, n = 5) or to one of six MGA treatment groups (n = 5 per group): 1) MGA administered orally each day via a gelatin capsule at a dose of 0.5 mg MGA/cow with the CL present (0.5CL); 2) 0.5 mg MGA/cow daily in the absence of CL (0.5NO); 3) 1.0 mg MGA with CL present (1.OCL); 4) 1.0 mg MGA without CL (1.ONO); 5) 1.5 mg MGA with CL present (1.5CL); 6) 1.5 mg without CL (1.5NO). MGA was administered for 10 days (Day 5 = initiation of treatment). To regress CL, cows assigned to groups without CL received injections of prostaglandin F2α (PGF, 0; 25 mg) on Days 6 and 7 of their estrous cycle. All cows were administered PGF2α. at the end of the 10-day treatment period. During the treatment period, daily blood samples were collected to determine concentrations of E2. Serial blood samples were collected at 15-min intervals for 24 h on Days 8, 11, and 14 to determine pattern of LH secretion. Frequency of LH pulses on Days 8, 11, and 14 was greater (p \u3c 0.05) in cows without CL (0.5NO, 1.ONO, and 1.5NO) than in cows with CL (0.5CL, 1.OCL, 1.5CL, and CONT). Mean concentrations of LH were greater (p \u3c 0.05) in cows from the 0.5NO group on Days 8 and 11 and were greater (p \u3c 0.05) in cows from the 0.5NO, 1.ONO, and 1.5NO groups on Day 14 as compared to cows with CL. Overall mean concentrations of LH across Days 8, 11, and 14 were greatest (p \u3c 0.05) in cows from the 0.5NO group and were also greater (p \u3c 0.05) in cows from the 0.5NO, 1.ONO, and 1.5NO groups as compared to cows in the 0.5CL, 1.OCL, 1.5CL, and CONT groups. Mean concentrations of E2 during the treatment period were greater (p \u3c 0.05) in cows from the 0.5NO group than in cows from either the 1.ONO or the 1.5NO group; these values were also greater (p \u3c 0.05) in cows of the 0.5NO, 1.ONO, and 1.5NO groups as compared to cows of the 1.OCL and CONT groups. Therefore, we reject our working hypothesis because doses of MGA greater than those typically used in estrous synchrony protocols did not suppress LH and E2 to the same extent that endogenous P4 does. In addition, MGA treatment when CL were present did not result in a further suppression of LH pulse frequency or of E2 as compared to the values in control cows with functional CL

    Final Report, Validation of Novel Planar Cell Design for MW-Scale SOFC Power Systems

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    This report describes the work completed by NexTech Materials, Ltd. during a three-year project to validate an electrolyte-supported planar solid oxide fuel cell design, termed the FlexCell, for coal-based, megawatt-scale power generation systems. This project was focused on the fabrication and testing of electrolyte-supported FlexCells with yttria-stabilized zirconia (YSZ) as the electrolyte material. YSZ based FlexCells were made with sizes ranging from 100 to 500 cm2. Single-cell testing was performed to confirm high electrochemical performance, both with diluted hydrogen and simulated coal gas as fuels. Finite element analysis modeling was performed at The Ohio State University was performed to establish FlexCell architectures with optimum mechanical robustness. A manufacturing cost analysis was completed, which confirmed that manufacturing costs of less than $50/kW are achievable at high volumes (500 MW/year)

    CYP2D6 Genotype is Not Associated with Survival in Breast Cancer Patients Treated with Tamoxifen: Results from a Population-based Study

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    Purpose: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Methods: Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). Results: CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). Conclusions: This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice

    A putative antiviral role of plant cytidine deaminases

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    [EN] Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions. Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes. This and control plants were then infected with CaMV. Virus accumulation and mutational spectra where characterized in both types of plants. Results: We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated. Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.This work was supported by the former Spanish Ministerio de Ciencia e Innovación-FEDER grant BFU2009-06993 to SFE. JMC was supported by the CSIC JAE-doc program/Fondo Social Europeo. AG-P was supported by a grant for Scientific and Technical Activities and by grant P10-CVI-65651, both from Junta de Andalucía.Martín, S.; Cuevas, J.; Grande-Perez, A.; Elena Fito, SF. (2017). A putative antiviral role of plant cytidine deaminases. F1000Research. 1-14. https://doi.org/10.12688/f1000research.11111.2S11

    Efficient CO2-Reducing Activity of NAD-Dependent Formate Dehydrogenase from Thiobacillus sp KNK65MA for Formate Production from CO2 Gas

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    NAD-dependent formate dehydrogenase (FDH) from Candida boidinii (CbFDH) has been widely used in various CO2 reduction systems but its practical applications are often impeded due to low CO2-reducing activity. In this study, we demonstrated superior CO2-reducing properties of FDH from Thiobacillus sp. KNK65MA (TsFDH) for production of formate from CO2 gas. To discover more efficient CO2-reducing FDHs than a reference enzyme e. CbFDH, five FDHs were selected with biochemical properties and then, their CO2-reducing activities were evaluated. All FDHs including CbFDH showed better CO2-reducing activities at acidic pHs than at neutral pHs and four FDHs were more active than CbFDH in the CO2 reduction reaction. In particular, the FDH from Thiobacillus sp. KNK65IVIA (TsFDH) exhibited the highest CO2-reducing activity and had a dramatic preference for the reduction reaction, i.e., a 84.2-fold higher ratio of CO2 reduction to formate oxidation in catalytic efficiency (k(cat)/K-B) compared to CbFDH. Formate was produced from CO2 gas using TsFDH and CbFDH, and TsFDH showed a 5.8-fold higher formate production rate than CbFDH. A sequence and structural comparison showed that FDHs with relatively high CO2-reducing activities had elongated N- and C-terminal loops. The experimental results demonstrate that TsFDH can be an alternative to CbFDH as a biocatalyst in CO2 reduction systemsope

    Distributed Drug Discovery, Part 2: Global Rehearsal of Alkylating Agents for the Synthesis of Resin-Bound Unnatural Amino Acids and Virtual D3 Catalog Construction

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    The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

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    Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores
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