821 research outputs found

    17beta-oestradiol and Enovid mammary tumorigenesis in C3H/HeJ female mice: counteraction by concurrent 2-bromo-alpha-ergocryptine.

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    Chronic administration of 17beta-oestradiol (via drinking water) or the oral contraceptive Enovid (norethynodrel and mestranol) (0-1 mg injected s.c. twice weekly) to nulliparous C3H/HeJ female mice, beginning at one month of age and terminating at 20 months (17beta-oestradiol) or 22 months (Enovid), significantly increased the incidence of mammary tumours over solvent-treated controls. Concurrent treatment of the steroid-treated mice with 2-bromo-alpha-ergocryptine (CB-154) (0-1 mg s.c. injected daily) significantly reduced mammary tumour incidence and mammary hyperplastic nodule development to the control level. CB-154 is an efficacious inhibitor of pituitary prolactin secretion. These results demonstrate that steroid-induced mammary gland dysplasias can be sharply reduced by chronic CB-154 treatment, and suggest that some of the mammary tumorigenic activities of oestrogenic steroids in C3H mice are mediated via an increased secretion of pituitary prolactin

    Stability conditions and positivity of invariants of fibrations

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    We study three methods that prove the positivity of a natural numerical invariant associated to 11-parameter families of polarized varieties. All these methods involve different stability conditions. In dimension 2 we prove that there is a natural connection between them, related to a yet another stability condition, the linear stability. Finally we make some speculations and prove new results in higher dimension.Comment: Final version, to appear in the Springer volume dedicated to Klaus Hulek on the occasion of his 60-th birthda

    Fibrations on four-folds with trivial canonical bundles

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    Four-folds with trivial canonical bundles are divided into six classes according to their holonomy group. We consider examples that are fibred by abelian surfaces over the projective plane. We construct such fibrations in five of the six classes, and prove that there is no such fibration in the sixth class. We classify all such fibrations whose generic fibre is the Jacobian of a genus two curve.Comment: 28 page

    Glassy-State Stabilization of a Dominant Negative Inhibitor Anthrax Vaccine Containing Aluminum Hydroxide and Glycopyranoside Lipid A Adjuvants

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    During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, Dominant Negative Inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40 °C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40 °C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40 °C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40 °C was observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose

    Taking up the cudgels against gay rights? Trends and trajectories in African Christian theologies on homosexuality

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    Against the background of the HIV epidemic and the intense public controversy on homosexuality in African societies, this article investigates the discourses of academic African Christian theologians on homosexuality. Distinguishing some major strands in African theology, that is, inculturation, liberation, women’s and reconstruction theology, the article examines how the central concepts of culture, liberation, justice, and human rights function in these discourses. On the basis of a qualitative analysis of a large number of publications, the article shows that stances of African theologians are varying from silence and rejection to acceptance. Although many African theologians have taken up the cudgels against gay rights, some “dissident voices” break the taboo and develop more inclusive concepts of African identity and African Christianity

    Campana points of bounded height on vector group compactifications

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    We initiate a systematic quantitative study of subsets of rational points that are integral with respect to a weighted boundary divisor on Fano orbifolds. We call the points in these sets Campana points. Earlier work of Campana and subsequently Abramovich shows that there are several reasonable competing definitions for Campana points. We use a version that delineates well different types of behaviour of points as the weights on the boundary divisor vary. This prompts a Manin-type conjecture on Fano orbifolds for sets of Campana points that satisfy a klt (Kawamata log terminal) condition. By importing work of Chambert-Loir and Tschinkel to our set-up, we prove a log version of Manin's conjecture for klt Campana points on equivariant compactifications of vector groups.Comment: 52 pages; minor revision, changes in the definition of Campana point

    Contribution of Cell Elongation to the Biofilm Formation of Pseudomonas aeruginosa during Anaerobic Respiration

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    Pseudomonas aeruginosa, a gram-negative bacterium of clinical importance, forms more robust biofilm during anaerobic respiration, a mode of growth presumed to occur in abnormally thickened mucus layer lining the cystic fibrosis (CF) patient airway. However, molecular basis behind this anaerobiosis-triggered robust biofilm formation is not clearly defined yet. Here, we identified a morphological change naturally accompanied by anaerobic respiration in P. aeruginosa and investigated its effect on the biofilm formation in vitro. A standard laboratory strain, PAO1 was highly elongated during anaerobic respiration compared with bacteria grown aerobically. Microscopic analysis demonstrated that cell elongation likely occurred as a consequence of defective cell division. Cell elongation was dependent on the presence of nitrite reductase (NIR) that reduces nitrite (NO2−) to nitric oxide (NO) and was repressed in PAO1 in the presence of carboxy-PTIO, a NO antagonist, demonstrating that cell elongation involves a process to respond to NO, a spontaneous byproduct of the anaerobic respiration. Importantly, the non-elongated NIR-deficient mutant failed to form biofilm, while a mutant of nitrate reductase (NAR) and wild type PAO1, both of which were highly elongated, formed robust biofilm. Taken together, our data reveal a role of previously undescribed cell biological event in P. aeruginosa biofilm formation and suggest NIR as a key player involved in such process

    Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.

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    The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococcal mutants. Streptonigrin (0.025 microgram/ml) efficiently killed gonococcal strain FA1090, and this effect depended on iron. Streptonigrin-resistant mutant FA6271 had normal iron uptake but was moderately deficient in total iron. Resistance most likely resulted from failure of FA6271 to divert electrons to streptonigrin, as demonstrated by a reduction in KCN-insensitive respiration (a hallmark of the action of quinones) and superoxide formation. Other mutants selected for inability to use human iron-binding proteins (strains FA6273 and FA6275) had no increase in streptonigrin MIC and no decrease in KCN-insensitive respiration. Mutants did not demonstrate an increase in superoxide dismutase or catalase. Streptonigrin killing of gonococci depended on a reaction(s) in which extracellular iron was important, presumably because iron was required for catalysis of hydroxyl radical. The results suggest that a membrane component may be a target for the actions of streptonigrin
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