Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim

What explains the uneven take-up of ISO 14001 at the global level?: a panel-data analysis

Since its release in the mid-1990s, close to 37 000 facilities have been certified to ISO 14001, the international voluntary standard for environmental management systems. Yet, despite claims that the standard can be readily adapted to very different corporate and geographic settings, its take-up has been highly geographically variable. This paper contributes to a growing body of work concerned with explaining the uneven diffusion of ISO 14001 at the global level. Drawing from the existing theoretical and empirical literature we develop a series of hypotheses about how various economic, market, and regulatory factors influence the national count of ISO 14001 certifications. These hypotheses are then tested using econometric estimation techniques with data for a panel of 142 developed and developing countries. We find that per capita ISO 14001 counts are positively correlated with income per capita, stock of foreign direct investment, exports of goods and services to Europe and Japan, and pressure from civil society. Conversely, productivity and levels of state intervention are negatively correlated. The paper finishes by offering a number of recommendations to policymakers concerned with accelerating the diffusion of voluntary environmental standards

Exponential Metric Fields

The Laser Interferometer Space Antenna (LISA) mission will use advanced technologies to achieve its science goals: the direct detection of gravitational waves, the observation of signals from compact (small and dense) stars as they spiral into black holes, the study of the role of massive black holes in galaxy evolution, the search for gravitational wave emission from the early Universe. The gravitational red-shift, the advance of the perihelion of Mercury, deflection of light and the time delay of radar signals are the classical tests in the first order of General Relativity (GR). However, LISA can possibly test Einstein's theories in the second order and perhaps, it will show some particular feature of non-linearity of gravitational interaction. In the present work we are seeking a method to construct theoretical templates that limit in the first order the tensorial structure of some metric fields, thus the non-linear terms are given by exponential functions of gravitational strength. The Newtonian limit obtained here, in the first order, is equivalent to GR.Comment: Accepted for publication in Astrophysics and Space Science, 17 page

Neurofibromin Deficient Myeloid Cells are Critical Mediators of Aneurysm Formation In Vivo

Background Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin, the protein product of NF1, functions as a negative regulator of Ras activity in circulating hematopoietic and vascular wall cells, which are critical for maintaining vessel wall homeostasis. NF1 patients have evidence of chronic inflammation resulting in development of premature cardiovascular disease, including arterial aneurysms, which may manifest as sudden death. However, the molecular pathogenesis of NF1 aneurysm formation is unknown. Method and Results Utilizing an angiotensin II-induced aneurysm model, we demonstrate that heterozygous inactivation of Nf1 (Nf1+/−) enhanced aneurysm formation with myeloid cell infiltration and increased oxidative stress in the vessel wall. Using lineage-restricted transgenic mice, we show loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1+/− aneurysm phenotype in vivo. Finally, oral administration of simvastatin or the antioxidant apocynin, reduced aneurysm formation in Nf1+/− mice. Conclusion These data provide genetic and pharmacologic evidence that Nf1+/− myeloid cells are the cellular triggers for aneurysm formation in a novel model of NF1 vasculopathy and provide a potential therapeutic target

Hysteresis, Avalanches, and Disorder Induced Critical Scaling: A Renormalization Group Approach

We study the zero temperature random field Ising model as a model for noise and avalanches in hysteretic systems. Tuning the amount of disorder in the system, we find an ordinary critical point with avalanches on all length scales. Using a mapping to the pure Ising model, we Borel sum the $6-\epsilon$ expansion to $O(\epsilon^5)$ for the correlation length exponent. We sketch a new method for directly calculating avalanche exponents, which we perform to $O(\epsilon)$. Numerical exponents in 3, 4, and 5 dimensions are in good agreement with the analytical predictions.Comment: 134 pages in REVTEX, plus 21 figures. The first two figures can be obtained from the references quoted in their respective figure captions, the remaining 19 figures are supplied separately in uuencoded forma

Determination of Inflationary Observables by Cosmic Microwave Background Anisotropy Experiments

Inflation produces nearly Harrison-Zel'dovich scalar and tensor perturbation spectra which lead to anisotropy in the cosmic microwave background (CMB). The amplitudes and shapes of these spectra can be parametrized by $Q_S^2$, $r\equiv Q_T^2/Q_S^2$, $n_S$ and $n_T$ where $Q_S^2$ and $Q_T^2$ are the scalar and tensor contributions to the square of the CMB quadrupole and $n_S$ and $n_T$ are the power-lawspectral indices. Even if we restrict ourselves to information from angles greater than one third of a degree, three of these observables can be measured with some precision. The combination $130^{1-n_S}Q_S^2$ can be known to better than $\pm 0.3\%$. The scalar index $n_S$ can be determined to better than $\pm 0.02$. The ratio $r$ can be known to about $\pm 0.1$ for $n_S \simeq 1$ and slightly better for smaller $n_S$. The precision with which $n_T$ can be measured depends weakly on $n_S$ and strongly on $r$. For $n_S \simeq 1$ $n_T$ can be determined with a precision of about $\pm 0.056(1.5+r)/r$. A full-sky experiment with a $20'$beam using technology available today, similar to those being planned by several groups, can achieve the above precision. Good angular resolution is more important than high signal-to-noise ratio; for a given detector sensitivity and observing time a smaller beam provides significantly more information than a larger beam. The uncertainties in $n_S$ and $r$ are roughly proportional to the beam size. We briefly discuss the effects of uncertainty in the Hubble constant, baryon density, cosmological constant and ionization history.Comment: 28 pages of uuencoded postscript with 8 included figures. A postscript version is also available by anonymous ftp at ftp://astro.uchicago.edu/pub/astro/knox/fullsim.p

Influence of antenatal physical exercise on haemodynamics in pregnant women: a flexible randomisation approach

Background: Normal pregnancy is associated with marked changes in haemodynamic function, however theinfluence and potential benefits of antenatal physical exercise at different stages of pregnancy and postpartumremain unclear. The aim of this study was therefore to characterise the influence of regular physical exercise onhaemodynamic variables at different stages of pregnancy and also in the postpartum period.Methods: Fifty healthy pregnant women were recruited and randomly assigned (2 × 2 × 2 design) to a land orwater-based exercise group or a control group. Exercising groups attended weekly classes from the 20th week ofpregnancy onwards. Haemodynamic assessments (heart rate, cardiac output, stroke volume, total peripheralresistance, systolic and diastolic blood pressure and end diastolic index) were performed using the Task Forcehaemodynamic monitor at 12–16, 26–28, 34–36 and 12 weeks following birth, during a protocol including posturalmanoeurvres (supine and standing) and light exercise.Results: In response to an acute bout of exercise in the postpartum period, stroke volume and end diastolic indexwere greater in the exercise group than the non-exercising control group (p = 0.041 and p = 0.028 respectively).Total peripheral resistance and diastolic blood pressure were also lower (p = 0.015 and p = 0.007, respectively) in theexercise group. Diastolic blood pressure was lower in the exercise group during the second trimester (p = 0.030).Conclusions: Antenatal exercise does not appear to substantially alter maternal physiology with advancinggestation, speculating that the already vast changes in maternal physiology mask the influences of antenatalexercise, however it does appear to result in an improvement in a woman’s haemodynamic function (enhancedventricular ejection performance and reduced blood pressure) following the end of pregnancy

Quantum dots coordinated with conjugated organic ligands: new nanomaterials with novel photophysics

CdSe quantum dots functionalized with oligo-(phenylene vinylene) (OPV) ligands (CdSe-OPV nanostructures) represent a new class of composite nanomaterials with significantly modified photophysics relative to bulk blends or isolated components. Single-molecule spectroscopy on these species have revealed novel photophysics such as enhanced energy transfer, spectral stability, and strongly modified excited state lifetimes and blinking statistics. Here, we review the role of ligands in quantum dot applications and summarize some of our recent efforts probing energy and charge transfer in hybrid CdSe-OPV composite nanostructures

The Effects of Two Types of Sleep Deprivation on Visual Working Memory Capacity and Filtering Efficiency

Sleep deprivation has adverse consequences for a variety of cognitive functions. The exact effects of sleep deprivation, though, are dependent upon the cognitive process examined. Within working memory, for example, some component processes are more vulnerable to sleep deprivation than others. Additionally, the differential impacts on cognition of different types of sleep deprivation have not been well studied. The aim of this study was to examine the effects of one night of total sleep deprivation and 4 nights of partial sleep deprivation (4 hours in bed/night) on two components of visual working memory: capacity and filtering efficiency. Forty-four healthy young adults were randomly assigned to one of the two sleep deprivation conditions. All participants were studied: 1) in a well-rested condition (following 6 nights of 9 hours in bed/night); and 2) following sleep deprivation, in a counter-balanced order. Visual working memory testing consisted of two related tasks. The first measured visual working memory capacity and the second measured the ability to ignore distractor stimuli in a visual scene (filtering efficiency). Results showed neither type of sleep deprivation reduced visual working memory capacity. Partial sleep deprivation also generally did not change filtering efficiency. Total sleep deprivation, on the other hand, did impair performance in the filtering task. These results suggest components of visual working memory are differentially vulnerable to the effects of sleep deprivation, and different types of sleep deprivation impact visual working memory to different degrees. Such findings have implications for operational settings where individuals may need to perform with inadequate sleep and whose jobs involve receiving an array of visual information and discriminating the relevant from the irrelevant prior to making decisions or taking actions (e.g., baggage screeners, air traffic controllers, military personnel, health care providers)

Color adjectives, standards, and thresholds: an experimental investigation

Are color adjectives (“red”, “green”, etc.) relative adjectives or absolute adjectives? Existing theories of the meaning of color adjectives attempt to answer that question using informal (“armchair”) judgments. The informal judgments of theorists conflict: it has been proposed that color adjectives are absolute with standards anchored at the minimum degree on the scale, that they are absolute but have near- midpoint standards, and that they are relative. In this paper we report two experiments, one based on entailment patterns and one based on presupposition accommodation, that investigate the meaning of scalar adjectives. We find evidence confirming the existence of subgroups of the population who operate with different standards for color adjectives. The evidence of interpersonal variation in where standards are located on the relevant scale and how those standards can be adjusted indicates that the existing theories of the meaning of color adjectives are at best only partially correct. We also find evidence that paradigmatic relative adjectives (“tall”, “wide”) behave in ways that are not predicted by the standard theory of scalar adjectives. We discuss several different possible explanations for this unexpected behavior. We conclude by discussing the relevance of our findings for philosophical debates about the nature and extent of semantically encoded context sensitivity in which color adjectives have played a key role