851 research outputs found

    The relationship of cyclic AMP levels and collagen synthesis in vascular smooth muscle cells following estrogen or beta-adrenergic treatment

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    The use of estrogens in postmenopausal women has become controversial. Estrogen replacement therapy has been used for many years to slow the progression of atherosclerosis. However, recent clinical studies have shown that menopausal women on hormone replacement therapy have higher incidences of myocardial infarctions and strokes than their counterparts without the therapy. Other studies have demonstrated that a decrease in collagen content in advanced atherosclerotic lesions may weaken the structural integrity of these lesions, resulting in rupture and clot formation. Within lesions, vascular smooth muscle cells (VSMCs) actively synthesize collagen and other types of extracellular matrix proteins during atherogenesis. Estrogen, through activation of the second messenger cAMP, may attenuate collagen synthesis in VSMCs and may promote reduction of collagen content in lesions. Incubation with Rp-cAMPs, a PKA inhibitor, blocked estrogen\u27s ability to inhibit collagen synthesis in VSMCs. This suggests that estrogen, through stimulation of cAMP, may activate the cAMP-PKA pathway in VSMCs. Treatment of VSMCs with estrogen and phophodiesterase inhibitors, cilostamide or Ro-20-1724, had an additive effect on increasing cAMP levels and on inhibiting collagen synthesis. VSMCs treated with estrogen and forskolin, an adenylyl cyclase stimulator, also had an additive effect on increasing cAMP levels and on attenuating collagen synthesis. When VSMCs were treated with both estrogen and a beta-adrenergic agonist, isoproterenol or terbutaline, there was an additive effect on cellular cAMP levels although the observed decrease in collagen synthetic rates were the same as observed in estrogen treated cells. VSMCs, which were treated with terbutaline, had a significantly higher amount of cAMP located extracellularly compared to estrogen treated cells. The different distribution patterns of cAMP observed in terbutaline and estrogen treated cells may explain why beta agonists may not attenuate collagen synthesis in VSMCs. These results clearly demonstrate that not all agents, which elevate cAMP, may inhibit collagen synthesis in VSMCs. Our data also suggest that the combination of agents, which have an additive effect with estrogen, may have a negative effect on the stability of existing atherosclerotic lesions through the inhibition of collagen synthesis

    An organizational systems perspective to business process modeling in small to medium enterprises (smes) : a case of food production

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    Taking an organizational systems perspective, this paper presents a review to business process modelling and examines the case of food manufacture in a Small to Medium Sized Enterprise (SME), which operates in Cyprus. As a result of the modelling and analysis carried out, areas of concern, issues and opportunities are identified and explored taking into consideration the current business environment of the SME, by focusing on the decision making processes of the production and scheduling activities. The knowledge gained from the modelling effort provides a deeper understanding of the operations and interrelationships between important processes such as “Make”, “Buy”, “Sell” and “Manage”. This proves to be useful for the effective re-design of a production/scheduling decision support system in the particular firm but it also represents the first step towards for the long term development of a generic framework for managerial decision making which takes into consideration the limitations and particularities of manufacturing SMEs.peer-reviewe

    Curvaton Dynamics

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    In contrast to the inflaton's case, the curvature perturbations due to the curvaton field depend strongly on the evolution of the curvaton before its decay. We study in detail the dynamics of the curvaton evolution during and after inflation. We consider that the flatness of the curvaton potential may be affected by supergravity corrections, which introduce an effective mass proportional to the Hubble parameter. We also consider that the curvaton potential may be dominated by a quartic or by a non-renormalizable term. We find analytic solutions for the curvaton's evolution for all these possibilities. In particular, we show that, in all the above cases, the curvaton's density ratio with respect to the background density of the Universe decreases. Therefore, it is necessary that the curvaton decays only after its potential becomes dominated by the quadratic term, which results in (Hubble damped) sinusoidal oscillations. In the case when a non-renormalizable term dominates the potential, we find a possible non-oscillatory attractor solution that threatens to erase the curvature perturbation spectrum. Finally, we study the effects of thermal corrections to the curvaton's potential and show that, if they ever dominate the effective mass, they lead to premature thermalization of the curvaton condensate. To avoid this danger, a stringent bound has to be imposed on the coupling of the curvaton to the thermal bath.Comment: 24 pages, 3 Postscript figures, RevTe

    Molecular analysis of photic inhibition of blood-feeding in Anopheles gambiae

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    <p>Abstract</p> <p>Background</p> <p><it>Anopheles gambiae </it>mosquitoes exhibit an endophilic, nocturnal blood feeding behavior. Despite the importance of light as a regulator of malaria transmission, our knowledge on the molecular interactions between environmental cues, the circadian oscillators and the host seeking and feeding systems of the <it>Anopheles </it>mosquitoes is limited.</p> <p>Results</p> <p>In the present study, we show that the blood feeding behavior of mosquitoes is under circadian control and can be modulated by light pulses, both in a clock dependent and in an independent manner. Short light pulses (~2–5 min) in the dark phase can inhibit the blood-feeding propensity of mosquitoes momentarily in a clock independent manner, while longer durations of light stimulation (~1–2 h) can induce a phase advance in blood-feeding propensity in a clock dependent manner. The temporary feeding inhibition after short light pulses may reflect a masking effect of light, an unknown mechanism which is known to superimpose on the true circadian regulation. Nonetheless, the shorter light pulses resulted in the differential regulation of a variety of genes including those implicated in the circadian control, suggesting that light induced masking effects also involve clock components. Light pulses (both short and long) also regulated genes implicated in feeding as well as different physiological processes like metabolism, transport, immunity and protease digestions. RNAi-mediated gene silencing assays of the light pulse regulated circadian factors <it>timeless</it>, <it>cryptochrome </it>and three <it>takeout </it>homologues significantly up-regulated the mosquito's blood-feeding propensity. In contrast, gene silencing of light pulse regulated olfactory factors down-regulated the mosquito's propensity to feed on blood.</p> <p>Conclusion</p> <p>Our study show that the mosquito's feeding behavior is under circadian control. Long and short light pulses can induce inhibition of blood-feeding through circadian and unknown mechanisms, respectively, that involve the chemosensory system.</p

    Implication of the Mosquito Midgut Microbiota in the Defense against Malaria Parasites

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    Malaria-transmitting mosquitoes are continuously exposed to microbes, including their midgut microbiota. This naturally acquired microbial flora can modulate the mosquito's vectorial capacity by inhibiting the development of Plasmodium and other human pathogens through an unknown mechanism. We have undertaken a comprehensive functional genomic approach to elucidate the molecular interplay between the bacterial co-infection and the development of the human malaria parasite Plasmodium falciparum in its natural vector Anopheles gambiae. Global transcription profiling of septic and aseptic mosquitoes identified a significant subset of immune genes that were mostly up-regulated by the mosquito's microbial flora, including several anti-Plasmodium factors. Microbe-free aseptic mosquitoes displayed an increased susceptibility to Plasmodium infection while co-feeding mosquitoes with bacteria and P. falciparum gametocytes resulted in lower than normal infection levels. Infection analyses suggest the bacteria-mediated anti-Plasmodium effect is mediated by the mosquitoes' antimicrobial immune responses, plausibly through activation of basal immunity. We show that the microbiota can modulate the anti-Plasmodium effects of some immune genes. In sum, the microbiota plays an essential role in modulating the mosquito's capacity to sustain Plasmodium infection

    Perturbative Unification of Soft Supersymmetry--Breaking Terms

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    Perturbative unification of soft supersymmetry--breaking (SSB) parameters is proposed in Gauge-Yukawa unified models. The method, which can be applied in any finite order in perturbation theory, consists in searching for renormalization group invariant relations among the SSB parameters, which are consistent with perturbative renormalizability. For the minimal Gauge-Yukawa unified model based on SU(5)SU(5) we find that the low energy SSB sector contains a single arbitrary parameter, the unified gaugino mass. Within a certain approximation we find that the model predicts a superpartner spectrum which is consistent with the experimental data.Comment: 14 page

    3D numerical assessment of the progressive collapse resistance of a seismic-resistant steel building with post-tensioned beam-column connections

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    This paper presents the numerical assessment of the progressive collapse resistance of a seismic-resistant steel building with post-tensioned beam-column connections. The numerical simulations are carried out in 3D under a loss of column scenario. The 3D model considers the effect of the composite slab, where composite beams and their shear connectors are modeled with a combination of shell, beam and nonlinear connector elements. All the beam-column and beam-to-beam connections are modeled using nonlinear connector elements with appropriate failure criteria. Moreover, the steel frame for which a column is removed is modelled in full detail with the aid of 3D solid elements to accurately capture its local and global nonlinear behavior. Nonlinear static analyses are carried out to identify the failure modes of the building under a sudden loss of column scenario and investigate the effect of the floor slab on the overall progressive collapse resistance

    Continuous exposure to Plasmodium results in decreased susceptibility and transcriptomic divergence of the Anopheles gambiae immune system

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    <p>Abstract</p> <p>Background</p> <p><it>Plasmodium </it>infection has been shown to compromise the fitness of the mosquito vector, reducing its fecundity and longevity. However, from an evolutionary perspective, the impact of <it>Plasmodium </it>infection as a selective pressure on the mosquito is largely unknown.</p> <p>Results</p> <p>In the present study we have addressed the effect of a continuous <it>Plasmodium berghei </it>infection on the resistance to infection and global gene expression in <it>Anopheles gambiae</it>.</p> <p>Exposure of <it>A. gambiae </it>to <it>P. berghei</it>-infected blood and infection for 16 generations resulted in a decreased susceptibility to infection, altered constitutive expression levels for approximately 2.4% of the mosquito's total transcriptome and a lower basal level of immune genes expression, including several anti-<it>Plasmodium </it>factors. The infection-responsiveness for several defense genes was elevated in the <it>P. berghei </it>exposed mosquito colonies.</p> <p>Conclusion</p> <p>Our study establishes the existence of a selective pressure exerted by the parasite <it>P. berghei </it>on the malaria vector <it>A. gambiae </it>that results in a decreased permissiveness to infection and changes in the mosquito transcriptome regulation that suggest a decreased constitutive immune gene activity but a more potent immune response upon <it>Plasmodium </it>challenge.</p
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