Evidence for involvement of both IKCa and SKCa channels in hyperpolarizing responses of the rat middle cerebral artery

Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IKCa channels alone, contrasting with peripheral vessels where block of both IKCa and SKCa is required. As the contribution of IKCa and SKCa to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SKCa might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions. METHODS: Rat middle cerebral arteries (approximately 175 microm) were mounted in a wire myograph. The effect of KCa channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 micromol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial KCa channels revealed with immunohistochemistry. RESULTS: SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IKCa (TRAM-34, 1 micromol/L) or SKCa (apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SKCa and IKCa within the endothelium. CONCLUSIONS: In the absence of NO, IKCa underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SKCa contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SKCa expression may be altered

Restricted Likelihood Ratio Tests in Predictive Regression

Chen and Deo (2009a) proposed procedures based on restricted maximum likelihood (REML) for estimation and inference in the context of predictive regression. Their method achieves bias reduction in both estimation and inference which assists in overcoming size distortion in predictive hypothesis testing. This paper provides extensions of the REML approach to more general cases which allow for drift in the predictive regressor and multiple regressors. It is shown that without modification the REML approach is seriously oversized and can have unit rejection probability in the limit under the null when the drift in the regressor is dominant. A limit theory for the modified REML test is given under a localized drift specification that accommodates predictors with varying degrees of persistence. The extension is useful in empirical work where predictors typically involve stochastic trends with drift and where there are multiple regressors. Simulations show that with these modifications, the good performance of the restricted likelihood ratio test (RLRT) is preserved and that RLRT outperforms other predictive tests in terms of size and power even when there is no drift in the regressor

Mechanically coupled laminates with balanced plain weave

Definitive listings of laminate stacking sequences are derived for balanced plain weave laminated materials, assuming each layer is composed of the same material with constant thickness throughout and that standard ply angle orientations 0, 90, and ±45° are adopted; consistent with industrial design practice. A single layer of balanced plain weave material is shown to be immune to thermal distortion following a standard high temperature manufacturing process, which implies that all laminates constructed of this material possess what is commonly referred to as the hygro-thermally curvature-stable or warp-free condition, irrespective of the individual ply orientations used or the laminate stacking sequence definition. A single uncoupled parent laminate class is shown to contain sub-groups with extensionally isotropic and fully isotropic properties that are invariant with off-axis orientation of the principal material axes with respect to the system or structural axes. By contrast a single mechanically coupled parent laminate class is shown to give rise to seven unique forms of coupled laminate through judicious off-axis orientation. Invariant off-axis properties are also identified in coupled laminate designs. Finally, example calculations, abridged stacking sequence listings and design data are presented

Health Utilities Associated with Hemoglobin Levels and Blood Loss in Postmenopausal Women: The Women's Health Initiative

AbstractObjectivesThe purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies.MethodsHealth utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis.ResultsWomen with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure.ConclusionsLower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions

Comet Machholz (C/2004 Q2): morphological structures in the inner coma and rotation parameters

Extensive observations of comet C/2004 Q2 (Machholz) were carried out between August 2004 and May 2005. The images obtained were used to investigate the comet's inner coma features at resolutions between 350 and 1500 km/pixel. A photometric analysis of the dust outflowing from the comet's nucleus and the study of the motion of the morphological structures in the inner coma indicated that the rotation period of the nucleus was most likely around 0.74 days. A thorough investigation of the inner coma morphology allowed us to observe two main active sources on the comet's nucleus, at a latitude of +85{\deg} \pm 5{\deg} and +45{\deg} \pm 5{\deg}, respectively. Further sources have been observed, but their activity ran out quite rapidly over time; the most relevant was at latcom. = 25{\deg} \pm 5{\deg}. Graphic simulations of the geometrical conditions of observation of the inner coma were compared with the images and used to determine a pole orientation at RA=95{\deg} \pm 5{\deg}, Dec=+35{\deg} \pm 5{\deg}. The comet's spin axis was lying nearly on the plane of the sky during the first decade of December 2004.Comment: 29 pages, 8 figures, 3 table

Excited hadrons from improved interpolating fields

The calculation of quark propagators for Ginsparg-Wilson-type Dirac operators is costly and thus limited to a few different sources. We present a new approach for determining spatially optimized operators for lattice spectroscopy of excited hadrons. Jacobi smeared quark sources with different widths are combined to construct hadron operators with different spatial wave functions. We study the Roper state and excited rho and pion mesons.Comment: Lattice2004(spectrum), 3 pages, 1 figure, (LaTeX style file espcrc2.sty and AMS style files

Striped periodic minimizers of a two-dimensional model for martensitic phase transitions

In this paper we consider a simplified two-dimensional scalar model for the formation of mesoscopic domain patterns in martensitic shape-memory alloys at the interface between a region occupied by the parent (austenite) phase and a region occupied by the product (martensite) phase, which can occur in two variants (twins). The model, first proposed by Kohn and Mueller, is defined by the following functional: $${\cal E}(u)=\beta||u(0,\cdot)||^2_{H^{1/2}([0,h])}+ \int_{0}^{L} dx \int_0^h dy \big(|u_x|^2 + \epsilon |u_{yy}| \big)$$ where $u:[0,L]\times[0,h]\to R$ is periodic in $y$ and $u_y=\pm 1$ almost everywhere. Conti proved that if $\beta\gtrsim\epsilon L/h^2$ then the minimal specific energy scales like $\sim \min\{(\epsilon\beta/L)^{1/2}, (\epsilon/L)^{2/3}\}$, as $(\epsilon/L)\to 0$. In the regime $(\epsilon\beta/L)^{1/2}\ll (\epsilon/L)^{2/3}$, we improve Conti's results, by computing exactly the minimal energy and by proving that minimizers are periodic one-dimensional sawtooth functions.Comment: 29 pages, 3 figure

Joint task scheduling and multi-UAV deployment for aerial computing in emergency communication networks

This article studies mobile edge computing technologies enabled by unmanned aerial vehicles (UAVs) in disasters. First, considering that the ground servers may be damaged in emergency scenarios, we proposed an air-ground cooperation architecture based on ad-hoc UAV networks. We defined the system cost as the weighted sum of task delay and energy consumption because of different delay sensitivity and energy sensitivity tasks in emergency communication networks. Then, we formulated the system cost-minimization problem of task scheduling and multi-UAV deployments. To solve the proposed mixed integer nonlinear programming problem, we decomposed it to two sub-problems that were solved by proposing a swap matching-based task scheduling sub-algorithm and a successive convex approximation-based multi-UAV deployment sub-algorithm. Accordingly, we propose a joint optimization algorithm by iterating the two sub-algorithms to obtain a low complexity sub-optimal solution. Finally, the simulation results show that (i) the proposed algorithm converges in several iterations, and (ii) compared with the benchmark algorithms, the proposed algorithm has better performance of reducing task delay and energy consumption and achieves a good trade-off between them for diverse tasks

The Conformal Willmore Functional: a Perturbative Approach

The conformal Willmore functional (which is conformal invariant in general Riemannian manifold $(M,g)$) is studied with a perturbative method: the Lyapunov-Schmidt reduction. Existence of critical points is shown in ambient manifolds $(\mathbb{R}^3, g_\epsilon)$ -where $g_\epsilon$ is a metric close and asymptotic to the euclidean one. With the same technique a non existence result is proved in general Riemannian manifolds $(M,g)$ of dimension three.Comment: 34 pages; Journal of Geometric Analysis, on line first 23 September 201

Amyloid-ß and a-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing

The formation of reactive oxygen species (ROS) is linked to the pathogenesis of neurodegenerative diseases. Here we have investigated the effect of soluble and aggregated amyloid-ß (Aß) and a-synuclein (aS), associated with Alzheimer''s and Parkinson''s diseases, respectively, on the Cu2+-catalyzed formation of ROS in vitro in the presence of a biological reductant. We find that the levels of ROS, and the rate by which ROS is generated, are significantly reduced when Cu2+ is bound to Aß or aS, particularly when they are in their oligomeric or fibrillar forms. This effect is attributed to a combination of radical scavenging and redox silencing mechanisms. Our findings suggest that the increase in ROS associated with the accumulation of aggregated Aß or aS does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu2+ and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures