The role of scavenger receptors in oxidised low-density lipoprotein induced platelet hyperactivity

Increased platelet hyperactivity is a common consequence of hyperlipidemia and is associated with increased risk of acute coronary syndromes. Platelet interaction with oxidised low-density lipoprotein (oxLDL) is believed to play a crucial role in platelet hyperactivity, although the mechanisms underpinning this are poorly understood. The aims of this study was to further understand the effects of oxLDL on platelet function. We performed a detailed characterisation of the conditions of LDL oxidation that generated a biologically active group of particles. Using this LDL preparation we show that oxLDL caused platelet degranulation, shape change and aggregation. This occurred through ligation to the receptor CD36, shown via pharmaceutical and knockout mouse data, with other evidence suggesting a supporting role for lectin-like oxidised LDL receptor 1 (LOX- 1). OxLDL promoted adhesion to collagen, but not fibrinogen in human platelets, which was lost in murine platelets deficient in CD36. Interestingly, we found that whilst oxLDL did not promote thrombus formation on collagen, it reduced the effects of both cyclic guanosine monophosphate and cyclic adenosine signaling pathways on platelet thrombus formation. We next examined the mechanisms underpinning ability of oxLDL to alter platelet function. Using immunoblotting, we found a central role for tyrosine kinase signaling in oxLDL mediated activation of platelets. We showed inactivation of Src family kinases, spleen tyrosine kinase (Syk), phospholipase Cγ2 (PLCγ2) and phosphoinositide 3- kinase (PI3-K), using a range of established pharmaceutical inhibitors, prevented platelet spreading to oxLDL. We later focused on PLCγ2 in greater detail, showing the protein to be tyrosine phosphorylated in platelets in response to oxLDL. We attempted to confirm these results in PLCγ2 deficient mice, although these mice showed no altered response to the oxidised lipid KOdiA-PC, requiring further investigation. The findings of this report support previous findings of a tyrosine kinase dependent signalling pathway and offer novel insight into how oxLDL is able to affect platelet reactivity by modulation of the effects of endogenous inhibitors. In summary, this data could suggest that the primary effect of oxLDL is to change the balance between platelet activatory and inhibitory pathways and therefore reduce the threshold for platelet activation.[Thesis also includes article published in Blood journal: http://www.bloodjournal.org/content/125/17/2693DOI: 10.1182/blood-2014-05-574491

Turbulent Mixing in Stars: Theoretical Hurdles

A program is outlined, and first results described, in which fully three-dimensional, time dependent simulations of hydrodynamic turbulence are used as a basis for theoretical investigation of the physics of turbulence in stars. The inadequacy of the treatment of turbulent convection as a diffusive process is discussed. A generalization to rotation and magnetohydrodynamics is indicated, as are connection to simulations of 3D stellar atmospheres.Comment: 5 pages, 1 figure, IAU Symposium 265, 200

Turbulent Cells in Stars: I. Fluctuations in Kinetic Energy and Luminosity

Three-dimensional (3D) hydrodynamic simulations of shell oxygen burning (Meakin and Arnett, 2007b) exhibit bursty, recurrent fluctuations in turbulent kinetic energy. These are shown to be due to a general instability of the convective cell, requiring only a localized source of heating or cooling. Such fluctuations are shown to be suppressed in simulations of stellar evolution which use mixing-length theory (MLT). Quantitatively similar behavior occurs in the model of a convective roll (cell) of Lorenz (1963), which is known to have a strange attractor that gives rise to chaotic fluctuations in time of velocity and, as we show, luminosity. Study of simulations suggests that the behavior of a Lorenz convective roll may resemble that of a cell in convective flow. We examine some implications of this simplest approximation, and suggest paths for improvement. Using the Lorenz model as representative of a convective cell, a multiple-cell model of a convective layer gives total luminosity fluctuations which are suggestive of irregular variables (red giants and supergiants (Schwarzschild 1975)), and of the long secondary period feature in semi-regular AGB variables (Stothers 2010, Wood, Olivier and Kawaler 2004). This "tau-mechanism" is a new source for stellar variability, which is inherently non-linear (unseen in linear stability analysis), and one closely related to intermittency in turbulence. It was already implicit in the 3D global simulations of Woodward, Porter and Jacobs (2003). This fluctuating behavior is seen in extended 2D simulations of CNeOSi burning shells (Arnett and Meakin 2011b), and may cause instability which leads to eruptions in progenitors of core collapse supernovae PRIOR to collapse.Comment: 30 pages, 13 figure

Monitoring and Failure Analysis of Corroded Bridge Cables under Fatigue Loading Using Acoustic Emission Sensors

Cables play an important role in cable-stayed systems, but are vulnerable to corrosion and fatigue damage. There is a dearth of studies on the fatigue damage evolution of corroded cable. In the present study, the acoustic emission (AE) technology is adopted to monitor the fatigue damage evolution process. First, the relationship between stress and strain is determined through a tensile test for corroded and non-corroded steel wires. Results show that the mechanical performance of corroded cables is changed considerably. The AE characteristic parameters for fatigue damage are then established. AE energy cumulative parameters can accurately describe the fatigue damage evolution of corroded cables. The failure modes in each phase as well as the type of acoustic emission source are determined based on the results of scanning electron microscopy. The waveform characteristics, damage types, and frequency distribution of the corroded cable at different damage phases are collected. Finally, the number of broken wires and breakage time of the cables are determined according to the variation in the margin index

Turbulent Convection in Stellar Interiors. II. The Velocity Field

We analyze stellar convection with the aid of 3D hydrodynamic simulations, introducing the turbulent cascade into our theoretical analysis. We devise closures of the Reynolds-decomposed mean field equations by simple physical modeling of the simulations (we relate temperature and density fluctuations via coefficients); the procedure (CABS, Convection Algorithms Based on Simulations) is terrestrially testable and is amenable to systematic improvement. We develop a turbulent kinetic energy equation which contains both nonlocal and time dependent terms, and is appropriate if the convective transit time is shorter than the evolutionary time scale. The interpretation of mixing-length theory (MLT) as generally used in astrophysics is incorrect; MLT forces the mixing length to be an imposed constant. Direct tests show that the damping associated with the flow is that suggested by Kolmogorov. The eddy size is approximately the depth of the convection zone, and this dissipation length corresponds to the "mixing length". New terms involving local heating by turbulent dissipation should appear in the stellar evolution equations. The enthalpy flux ("convective luminosity") is directly connected to the buoyant acceleration, and hence the velocity scale. MLT tends to systematically underestimate this velocity scale. Quantitative comparison with a variety of 3D simulations reveals a previously recognized consistency. Examples of application to stellar evolution will be presented in subsequent papers in this series.Comment: 47 pages, 7 figures, accepted by Ap

Morphine modulation of pain processing in medial and lateral pain pathways

<p>Abstract</p> <p>Background</p> <p>Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording technique. Pain evoked neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with eight-wire microelectrode arrays in awake rats.</p> <p>Results</p> <p>The results showed that the noxious heat evoked responses of single neurons in all of the four areas were depressed after systemic injection of 5 mg/kg morphine. The depressive effects of morphine included (i) decreasing the neuronal response magnitude; (ii) reducing the fraction of responding neurons, and (iii) shortening the response duration. In addition, the capability of cortical and thalamic neural ensembles to discriminate noxious from innocuous stimuli was decreased by morphine within both pain pathways. Meanwhile, morphine suppressed the pain-evoked changes in the information flow from medial to lateral pathway and from cortex to thalamus. These effects were completely blocked by pre-treatment with the opiate receptor antagonist naloxone.</p> <p>Conclusion</p> <p>These results suggest that morphine exerts analgesic effects through suppressing both sensory and affective dimensions of pain.</p

Eye Care Providers' Attitudes Towards Tele-ophthalmology

Background: The rapid rise of e-health and remote care systems will likely change the practice patterns of ophthalmologists. Although telemedicine practices are thriving in many specialties of medicine, telemedicine for ophthalmology has been limited primarily to asynchronous care for diabetic retinopathy. The goal of this research was to evaluate perspectives on and familiarity with telemedicine among eye care providers at a large tertiary-care medical center via an anonymous, descriptive survey. Results: In total, 58 eye care physicians completed surveys (response rates of 86% for physicians-in-training and 49% for faculty physicians, respectively). Although a majority of both faculty and physicians-in-training were willing to participate in telemedicine services, trainees were more likely to be willing to interpret photographs than faculty (p=0.04). Most respondents (71%) indicated that they did not use telemedicine. Over half had received photographs (via phone or e-mail) for interpretation from referring physicians (54%) or patients (56%) within the past 3 months. A majority of providers (82%) would be willing to participate in telemedicine for consultations and for interpreting photographs, but a majority (59%) had low confidence in remote care for providing an opinion on patient care. Conclusions: Most eye care providers viewed telemedicine as part of the future of eye care but were concerned about the use of telemedicine. Although most providers did not practice telemedicine, over half of them were comfortable managing eye care consultations (including patients' photographs) via the Internet.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140282/1/tmj.2014.0115.pd