1,339 research outputs found

    The Messy Making Of David Jones's Anathemata

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    Parental rearing style as a predictor of attachment and psychosocial adjustment during young adulthood

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    Parental rearing-styles are crucial for psychosocial adjustment both during childhood and adulthood. The current study examined whether: (a) parental rearing-styles predicted psychosocial adjustment in young-adulthood, (b) this relationship was mediated by attachment styles , and ( c ) gender differences occur in these relationships. Two hundred and forty (103 male and 132 female) university students completed measures assessing parental rearing-style , current attachment style, romantic relationship satisfaction, friendship quality, self-esteem, and social competence. Multigroup structural equation modelling, conducted separately by gender, revealed that parental rearing-style predicted psychosocial adjustment during young-adulthood. Further, there was also evidence of gender differences and that self-models and other-models of attachment mediated this relationship. Together, these findings reinforce the importance of perceived parental rearing-style for subsequent psychosocial adjustment

    Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

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    BackgroundLobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.MethodsIn all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.ResultsOut of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.ConclusionOur study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection

    Newcastle disease virus degrades HIF-1a through proteasomal pathways independent of VHL and p53

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    Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated α (HIF-1α) and a constitutive β subunit (HIF-1β). To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study. Data obtained showed that a velogenic NDV infection diminished hypoxia-induced HIF-1α accumulation, leading to a decreased activation of its downstream target gene, carbonic anhydrase 9. This NDV-induced downregulation of HIF-1α occurred post-translationally and was partially abrogated by proteasomal inhibition. The process appeared to be independent of the tumour suppressor protein p53. These data revealed a correlation between NDV infection and HIF-1α downregulation, which highlights NDV as a promising agent to eliminate hypoxic cancer cells

    The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling

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    Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells

    A Revised Historical Light Curve of Eta Carinae and the Timing of Close Periastron Encounters

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    The historical light curve of the 19th century "Great Eruption" of etaCar provides a striking record of violent instabilies encountered by the most massive stars. We report and analyze newly uncovered historical estimates of the visual brightness of etaCar during its eruption, and we correct some mistakes in the original record. The revised light curve looks substantially different from previous accounts: it shows two brief eruptions in 1838 and 1843 that resemble modern supernova impostors, while the final brightening in December 1844 marks the time when etaCar reached its peak brightness. We consider the timing of brightening events as they pertain to the putative binary system in etaCar: (1) The brief 1838 and 1843 events peaked within weeks of periastron if the pre-1845 orbital period is shorter than at present due to the mass loss of the eruption. Each event lasted only 100 days. (2) The main brightening at the end of 1844 has no conceivable association with periastron, beginning more than 1.5yr afterward. It lasted 10yr, with no obvious influence of periastron encounters during that time. (3) The 1890 eruption began to brighten at periastron, but took over 1yr to reach maximum and remained there for almost 10yr. A second periastron passage midway through the 1890 eruption had no effect. While evidence for a link between periastron encounters and the two brief precursor events is compelling, the differences between the three cases above make it difficult to explain all three phenomena with the same mechanism.Comment: 11 pages, 4 figures. submitted to MNRAS on october 12. updated reference

    Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the EV71 VP1 fragment.

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    Enterovirus 71 (EV71) infection may cause severe neurological complications, particularly in young children. Despite the risks, there are still no commercially available EV71 vaccines. Hence, a candidate vaccine construct, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP1 1-100) protein, was evaluated in a mouse model of EV71 infection. Previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabbits. That study, however, did not address the issue of its effectiveness against EV71 infection in young animals. In the present study, EV71 viral challenge in vaccinated newborn mice resulted in more than 40% increase in survival rate. Significantly, half of the surviving mice fully recovered from their paralysis. Histological analysis of all of the surviving mice revealed a complete clearance of EV71 viral antigens from their brains and spinal cords. In hind limb muscles, the amounts of the antigens detected correlated with the degrees of tissue damage and paralysis. Findings from this study provide evidence that immunization with the NPt-VP1 1-100 immunogen in a newborn mouse model confers partial protection against EV71 infection, and also highlights the importance of NPt-VP1 1-100 as a possible candidate vaccine for protection against EV71 infections

    Lucy: Navigating a Jupiter Trojan Tour

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    In January 2017, NASA selected the Lucy mission to explore six Jupiter Trojan asteroids. These six bodies, remnants of the primordial material that formed the outer planets, were captured in the Sun-Jupiter L4 and L5 Lagrangian regions early in the solar system formation. These particular bodies were chosen because of their diverse spectral properties and the chance to observe up close for the first time two orbiting approximately equal mass binaries, Patroclus and Menoetius. KinetX, Inc. is the primary navigation supplier for the Lucy mission. This paper describes preliminary navigation analyses of the approach phase for each Trojan encounter
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