696 research outputs found

    Quantum Networks for Concentrating Entanglement

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    If two parties, Alice and Bob, share some number, n, of partially entangled pairs of qubits, then it is possible for them to concentrate these pairs into some smaller number of maximally entangled states. We present a simplified version of the algorithm for such entanglement concentration, and we describe efficient networks for implementing these operations.Comment: 15 pages, 2 figure

    NFκB and AP-1 Drive Human Myometrial IL8 Expression

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    The uterine expression of the chemokine IL8 increases dramatically with the onset of labour both at term and preterm. The IL8 promoter contains binding sites for the transcription factors nuclear factor-kappa B (NFκB), activator protein-1 (AP-1), and CCAAT/enhancer-binding protein (CEBP). In this study we investigated the roles of these transcription factors in IL1B regulation of the IL8 gene in human myometrium. Using chromatin immune precipitation (ChIP) assay, we showed that each of NFκB, CEBP, and AP-1 binds to the IL8 promoter upon IL1B stimulation. To examine the relative importance of each site in IL8 gene expression, site-directed mutagenesis of each of these sites was performed. We found that the NFκB site was essential for basal and IL1B-stimulated gene expression. Mutation of the AP-1 site reduced both basal and IL1B-stimulated expression but to a lesser extent. Mutation of the CEBP site had no effect upon basal expression but eliminated the IL1B response. Small interfering RNA (siRNA) silencing of NFκB abolished the IL8 response to IL1B significantly; siRNA against AP-1 reduced it to a lesser extent whilst knockdown of CEBP enhanced the response. Our data confirms a central and essential role for NFκB in regulation of IL8 in human myometrium

    The Th1:Th2 Dichotomy of Pregnancy and Preterm Labour

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    Pregnancy is a unique immunological state in which a balance of immune tolerance and suppression is needed to protect the fetus without compromising the mother. It has long been established that a bias from the T helper 1 cytokine profile towards the T helper 2 profile contributes towards successful pregnancy maintenance. The majority of publications that report on aberrant Th1:Th2 balance focus on early pregnancy loss and preeclampsia. Over the last few decades, there has been an increased awareness of the role of infection and inflammation in preterm labour, and the search for new biomarkers to predict preterm labour continues. In this paper, we explore the evidence for an aberrant Th1:Th2 profile associated with preterm labour. We also consider the potential for its use in screening women at high risk of preterm labour and for prophylactic therapeutic measures for the prevention of preterm labour and associated neonatal adverse outcomes

    Mesoarchaean collision of Kapisilik terrane 3070Ma juvenile arc rocks and \u3e3600Ma Isukasia terrane continental crust (Greenland)

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    The Mesoarchaean Kapisilik and Eoarchaean Isukasia terranes in the Nuuk region of southern West Greenland were tectonically juxtaposed in the Archaean. The north of the Isukasia terrane is distal from the Kapisilik terrane and has only rare growth of ~2690Ma metamorphic zircon and no 2980-2950Ma metamorphic zircon. The southern part of the Isukasia terrane lies between two ~2690Ma shear zones, and has locally preserved high pressure granulite facies assemblages and widespread growth of 2980-2950Ma metamorphic zircon and also sporadic growth of ~2690Ma metamorphic zircon. Within this southern part of the Isukasia terrane there is a folded klippe of mylonitised Mesoarchaean detrital meta-sedimentary rocks (carrying \u3e3600 and ~3070Ma detrital zircons), mafic and ultramafic rocks, with ~2970Ma metamorphic zircon overgrowths. South of the Isukasia terrane is the Kapisilik terrane, containing ~3070Ma arc-related volcanic rocks, gabbro-anorthosites and meta-tonalites, intruded by 2970-2960Ma granites. Zircons of an Ivisârtoq supracrustal belt ~3075Ma intermediate volcanic rock have initial e{open}Hf values of +2 to +5 thus are juvenile crustal additions. ~3070Ma tonalites along the northern edge of the Kapisilik terrane have whole rock positive initial e{open}Nd values and thus are also juvenile crustal additions. In contrast, igneous zircons in 2960Ma granites intruded into juvenile ~3075Ma supracrustal rocks of the Kapisilik terrane have initial e{open}Hf values of -5 to -10, and must have involved the partial melting of \u3e3600Ma Isukasia terrane rocks.The integrated structural and zircon U-Th-Pb-Hf isotopic data show that at 2980-2950. Ma the Kapisilik terrane juvenile arc components collided with, and over-rid, the Isukasia terrane. The southern edge of the Isukasia terrane came to lie in the deep crust under the Ivisârtoq supracrustal belt and melted at 2970-2960. Ma to produce granites. These granites derived from ancient crust rose into the upper crust, where they intruded the overlying allochthonous juvenile ~3075. Ma Ivisârtoq supracrustal belt arc assemblages. The southern edge of the Isukasia terrane is interpreted as an interior nappe of Eoarchaean basement rocks interfolded with a klippe of Mesoarchaean metasedimentary and mafic/ultramafic rocks, both of which are affected by 2980-2950. Ma metamorphism. The mixed Eoarchaean-Mesoarchaean detrital provenance suggests that the klippe could be dismembered components of an accretionary prism or forearc crust. The northern part of the Isukasia terrane is interpreted as foreland, free of 2980-2950. Ma high-grade metamorphic overprint. This shows that the Isukasia terrane is not a coherent block, but contains ancient rocks that are parautochthonous or allochthonous to each other, with contrasting later metamorphic history.At ~2690. Ma the crustal architecture arisen from Mesoarchaean collision between an older continental block and an island arc was reworked along intra-crustal shear zones, coeval with amphibolite facies metamorphism. This reworking followed on from major terrane assembly at 2710-2700. Ma in the southern part of the Nuuk region, when the Eoarchaean Færingehavn terrane was juxtaposed with 2840-2825. Ma arc rocks. Thus the 2980-2950. Ma assembly of the Isukasia and Kapisilik terranes is distinct from the later 2710-2700. Ma terrane assembly further south in the Nuuk region

    Changes in the Th1 : Th2 Cytokine Bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2

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    Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ12,14-Prostaglandin J2 (15dPGJ2) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ2 or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4+ cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ2 reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2+ve cells. 15dPGJ2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL

    Specific inhibition of c-Jun N-terminal kinase delays preterm labour and reduces mortality

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    Preterm labour (PTL) is commonly associated with infection and/or inflammation. Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)/AP1- or NF-kB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK/AP-1 and NF-kB, showed that selective inhibition of NF-kB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK/AP-1 but not NF-kB, inhibition of JNK/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain

    Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes

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    The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF-κB activation. The negative interaction between NF-κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF-κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter-relationship, we have used small interfering (si) RNA-mediated knock-down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL-1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR-knock-down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR-induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro-inflammatory gene networks induced by IL-1β and that only MMP10 was significantly regulated in opposite directions by IL-1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR

    The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via Gαi signalling

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    Oxytocin (OT) plays an important role in the onset of human labour by stimulating uterine contractions and promoting prostaglandin/inflammatory cytokine synthesis in amnion via oxytocin receptor (OTR) coupling. The OTR-antagonist, Atosiban, is widely used as a tocolytic for the management of acute preterm labour. We found that in primary human amniocytes, Atosiban (10 μM) signals via PTX-sensitive Gαi to activate transcription factor NF-κB p65, ERK1/2, and p38 which subsequently drives upregulation of the prostaglandin synthesis enzymes, COX-2 and phospho-cPLA2 and excretion of prostaglandins (PGE2) (n = 6; p < 0.05, ANOVA). Moreover, Atosiban treatment increased expression and excretion of the inflammatory cytokines, IL-6 and CCL5. We also showed that OT-simulated activation of NF-κB, ERK1/2, and p38 and subsequent prostaglandin and inflammatory cytokine synthesis is via Gαi−2 and Gαi−3 but not Gαq, and is not inhibited by Atosiban. Activation or exacerbation of inflammation is not a desirable effect of tocolytics. Therefore therapeutic modulation of the OT/OTR system for clinical management of term/preterm labour should consider the effects of differential G-protein coupling of the OTR and the role of OT or selective OTR agonists/antagonists in activating proinflammatory pathways

    Regenerative Fuel Cell Power Systems for Lunar and Martian Surface Exploration

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    This paper presents the preliminary results of a recent National Aeronautics and Space Administration (NASA) study funded under the Advanced Exploration Systems (AES) Modular Power Systems (AMPS) project. This study evaluated multiple surface locations on both the Moon and Mars, with the goal of establishing a common approach towards technology development and system design for surface power systems that use Regenerative Fuel Cell (RFC) energy storage methods. One RFC design may not be applicable to all surface locations; however, AMPS seeks to find a unified architecture, or series of architectures, that leverages a single development approach to answer the technology need for RFC systems. Early system trades were performed to select the most effective fuel cell and electrolyzer architectures based on current state-of-the-art technology, whereas later trades will establish a detailed system design to enable a near-term ground (non-flight) demonstration. This paper focuses on the initial trade studies, presents the selected fuel cell and electrolyzer architectures for follow-on system design studies, and suggests areas for further technology investment
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