376 research outputs found

    Pojetí revoluce v díle N. A. Berďajeva

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    Tato práce se věnuje studiu pojetí revoluce v díle ruského filosofa N.A. Berd'ajeva. Nejprve je načrtnuta celková charakteristika díla tohoto filosofa a zvláštní pozornost je věnována jeho stylu. Hlavním cílem práce je popsat Berd'ajevův vztah k samotnému pojmu revoluce z filo- sofického, sociologického a historiosofického pohledu a dát ho do souvislosti s historickými událostmi první čtvrtiny 20. století v Rusku. K tomu jsou použity Berd'ajevovy statě ve sbornících Problémy idealismu, Milníky (Věchy) a De profundis (Iz glubiny) a dále jeho práce Duchovní krize inteligence, Duchovní základy ruské revoluce a Filosofie nerovnosti.This thesis is focused on a concept of revolution in writings of Russian philosopher Nikolai Berdyaev. It starts with general characteristics of a philosopher's works and special attention is given to the style of his writing. Main objective of the thesis is a description of Berdyaev's relation to the term revolution itself, which is given from philosophical, sociological and his- toriosophical perspective, as well as putting his notion of revolution into the context of histor- ical events that has occurred during the first quarter of 20th century in Russia. Thesis draws on Berdyaev's articles that appeared in these collections of papers: The Problems of Idealism (Problemy idealizma), Signposts (Vekhi), De profundis (Iz glubiny) and on his works: The Spir- itual Crisis of the Intelligentsia, The Philosophy of Inequality, The Spiritual Origins of Russian Revolution.Institute of East European StudiesÚstav východoevropských studiíFaculty of ArtsFilozofická fakult

    An algorithmic approach to resolutions

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    We provide an algorithmic method for constructing projective resolutions of modules over quotients of path algebras. This algorithm is modified to construct minimal projective resolutions of linear modules over Koszul algebras

    Phorbol 12-Myristate 13-Acetate Stimulates Lysophosphatidic Acid Secretion from Ovarian and Cervical Cancer Cells but Not From Breast or Leukemia Cells

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    Lysophosphatidic acid (LPA) is present in ascites from patients with ovarian cancer. It stimulates calcium release and growth of ovarian cancer cells bothin vitroandin vivo.Recently, we found that LPA levels were significantly elevated in plasma from patients with ovarian cancer and other gynecological cancers. In contrast, LPA levels were not elevated in patients with breast cancer and leukemias. In view of this, we investigated whether gynecological cancer cells could produce LPA. LPA was extracted from the supernatant of cells culturedin vitroand purified by thin layer chromatography. After hydrolysis and transmethylation, the fatty acid derivatives were analyzed by gas chromatography. We found that the phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly stimulated the production of LPA in ovarian and cervical cancer cells. In contrast, a small or negligible amount of LPA was produced in breast cancer and leukemia cells upon PMA stimulation. This cell type specificity correlates with our values of plasma LPA, suggesting that gynecological tumor cells may be an important source of the elevated LPA noted in the plasma of patients with these cancers. The cytosolic PLA2(cPLA2)/Ca2+-independent PLA2(iPLA2) inhibitor, AACOCF3, inhibited 75.6% PMA-stimulated LPA secretion in ovarian cancer cells, suggesting a cPLA2/iPLA2activity was involved in LPA production from ovarian cancer cells

    Phorbol 12-Myristate 13-Acetate Stimulates Lysophosphatidic Acid Secretion from Ovarian and Cervical Cancer Cells but Not From Breast or Leukemia Cells

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    Lysophosphatidic acid (LPA) is present in ascites from patients with ovarian cancer. It stimulates calcium release and growth of ovarian cancer cells bothin vitroandin vivo.Recently, we found that LPA levels were significantly elevated in plasma from patients with ovarian cancer and other gynecological cancers. In contrast, LPA levels were not elevated in patients with breast cancer and leukemias. In view of this, we investigated whether gynecological cancer cells could produce LPA. LPA was extracted from the supernatant of cells culturedin vitroand purified by thin layer chromatography. After hydrolysis and transmethylation, the fatty acid derivatives were analyzed by gas chromatography. We found that the phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly stimulated the production of LPA in ovarian and cervical cancer cells. In contrast, a small or negligible amount of LPA was produced in breast cancer and leukemia cells upon PMA stimulation. This cell type specificity correlates with our values of plasma LPA, suggesting that gynecological tumor cells may be an important source of the elevated LPA noted in the plasma of patients with these cancers. The cytosolic PLA2(cPLA2)/Ca2+-independent PLA2(iPLA2) inhibitor, AACOCF3, inhibited 75.6% PMA-stimulated LPA secretion in ovarian cancer cells, suggesting a cPLA2/iPLA2activity was involved in LPA production from ovarian cancer cells

    Association of Reproductive History with Human Papillomavirus and Cervical Intraepithelial Neoplasia Severity

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    Our objective was to uncover potential links between Human Papillomavirus infection, common reproductive outcomes and high-grade cervical pre-cancer. We evaluated common reproductive risk factors, by varied stratifications of histologic grade, among 2,055 women positive and 6,657 women negative for Human Papillomavirus (HPV), who were enrolled in the Shanxi Province Cervical Cancer Screening Study II. Logistic regression was used to generate odds ratios and their corresponding 95% confidence intervals. Risk-factor profiles diverged for Cervical Intraepithelial Neoplasia (CIN) II compared to CIN III, but were broadly similar for CIN II compared to CIN I. An increased risk of CIN III versus CIN II was seen for higher gravidity (≥ 3 pregnancies) [odds ratio (OR)=1.6 (95% confidence interval [CI]: 1.0, 2.6)] and sexual intercourse within four months of childbirth [OR=2.0 (1.3, 3.2)]. Risks associated with reproductive factors appeared comparable for CIN II and CIN I, except an inverse association observed for sexual intercourse within four months of childbirth for CIN II versus CIN I [OR= 0.64 (0.42, 0.97)]. If CIN III and CIN II are biologically similar, risk-factor profiles would be expected to be more similar between CIN III and CIN II. Instead, risk factor profiles between CIN II and CIN I were more similar. Utilizing these results, we investigated a broader spectrum of reproductive risk factors for CIN III versus ≤ CIN II. Higher gravidity (≥ 3 pregnancies) was associated with higher risk of CIN III versus ≤ CIN II [OR=1.5 (1.0, 2.1)], as was intercourse within four months of childbirth [OR=1.7 (1.2, 2.3)], and age. It is biologically plausible that elevated levels of hormones during pregnancy or immediately postpartum may act as promoters in cervical carcinogenesis, aiding the progression of cervical disease. These results add to the accumulating evidence that CIN II may be biologically more similar to CIN I than to CIN III, and that reproductive co-factors play an important role in the progression of HPV to high-grade pre-cancer. These results can provide impetus for investigators with prospective data to follow-up women with CIN II, and to analyze risk factors by histological grade

    ApoE4-Driven Accumulation of Intraneuronal Oligomerized Aβ42 following Activation of the Amyloid Cascade In Vivo Is Mediated by a Gain of Function

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    Activating the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin in targeted replacement mice, which express either apoE4 or apoE3, results in the specific accumulation of oligomerized Aβ42 in hippocampal CA1 neurons of the apoE4 mice. We presently investigated the extent to which the apoE4-driven accumulation of Aβ42 and the resulting mitochondrial pathology are due to either gain or loss of function. This revealed that inhibition of neprilysin for one week triggers the accumulation of Aβ42 in hippocampal CA1 neurons of the apoE4 mice but not of either the corresponding apoE3 mice or apoE-deficient mice. At 10 days, Aβ42 also accumulated in the CA1 neurons of the apoE-deficient mice but not in those of the apoE3 mice. Mitochondrial pathology, which in the apoE4 mice is an early pathological consequence following inhibition of neprilyisn, also occurs in the apoE-deficient but not in the apoE3 mice and the magnitude of this effect correlates with the levels of accumulated Aβ42 and oligomerized Aβ42 in these mice. These findings suggest that the rate-limiting step in the pathological effects of apoE4 on CA1 neurons is the accumulation of intracellular oligomerized Aβ42 which is mediated via a gain of function property of apoE4

    Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method

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    BackgroundWorldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.MethodsWe compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.ResultsOf 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing.ConclusionsThe sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening

    Mailed Human Papillomavirus Self-Collection With Papanicolaou Test Referral for Infrequently Screened Women in the United States

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    Testing for high-risk human papillomavirus (HPV) infection using mailed, self-collected samples is a promising approach to increase screening in women who do not attend clinic screening at recommended intervals

    Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women

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    To optimize HPV vaccination implementation at the population-level in China, data are needed on age-specific HPV 16, 18, 6 and 11 prevalence. This cross-sectional, population-based study evaluated the age- and type-specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17-54 year old women from three rural provinces (Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid-based cervical cytology (SurePath). High- and low-risk HPV types were detected with HC-II (Qiagen), with genotyping of HPV-positive samples using Linear Array (Roche). HPV 16, 18, 6 and 11 serum antibodies were detected using a Luminex-based, competitive immunoassay (Merck). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30-34 (4.2%) and 45-49 yr (3.8%), while HPV 18 DNA prevalence peaked at ages 40-44 yr (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing age. Cumulative exposure of HPV may be underreported in this population, as cross-sectional data do not accurately reflect exposure to HPV infections over time
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