AR Signal Research Articles

Developmental regulation of the male urogenital papilla in the male marine teleost black rockfish, Sebastes schlegelii (Hilgendorf, 1880).

The male external genitalia of the black rockfish (Sebastes schlegelii Hilgendorf, 1880) is a fleshy protrusion known as the urogenital papilla (UGP), which functions to deliver sperm into the female reproductive tract for internal fertilization. It is not known which genes regulate the development of the UGP. The aim of this study was to identify key genes that regulate the development of the UGP in black rockfish and to determine the distribution of androgen receptor gene (ar) in the UGP. A total of twenty-six adult males and 560 juvenile fish were used in the experiment, in which we divided all normally developing juveniles into normal development and androgen groups. We added methyltestosterone solution (100 ug/L) to the androgen group-treated fish tank, soaked for 2hours per day for 38days, and sampled 5 ~ 10 samples each time every 5days during the culture process. Gene expression changes related to urogenital papilla were analyzed with tissue specificity between control and androgen groups during sex differentiation, adult male maturation, and the copulation stage (September to December) using Real Time Quantitative PCR (RT-qPCR). The expression of ar (ara and arb) was also localized by two-color in situ hybridization in the UGP region of juvenile fish. Androgen treatment enhanced ar expression levels and the ar signal was stronger in the UGP region of both adult breeding fish and androgen-treated juvenile fish. This study provides insights into the regulation of the external genitalia of black rockfish and presents vital information for the artificial breeding of viviparous fish.

Data intrinsic correction for working distance variations in MA‐XRF of historical paintings based on the Ar signal

The nonplanar shape of a painting as well as practical constraints often result in the painting's surface not being parallel to the plane in that the measurement head of a MA‐XRF scanner is being moved. Changing the working distance affects the measurement geometry, so that the sensitivity for the same element may vary throughout the investigated area and induce visible artifacts. These artifacts are especially visible when different scans of the same painting are stitched together. In this article, we present an approach to correct for the variation of the measurement distance. We explored using an intrinsic part of the XRF data set, the Ar signal from the air, to estimate the distance between surface and instrument. The model is developed based on fundamental parameter calculations and a measurement of a NIST 610 standard and is verified on a set of scans of Rembrandt's ‘Portrait of Oopjen Coppit (1611–1689)’.

THE TISSUE COMMON RESPONSE MODULE (TCRM) SCORE PROVIDES A QUANTITATIVE OBJECTIVE BIOPSY SCORE TO ASSESS THE SEVERITY OF PANCREAS TRANSPLANT REJECTION

Introduction: Several studies have used gene expression profiling to identify key immunologic and inflammatory markers in the blood and tissue of solid-organ transplant recipients experiencing rejection (AR), but none of these have included samples from pancreas transplant (PT) recipients. Gene expression analysis of public transcriptional data from kidney, heart, liver, and lung transplant rejection led to the tissue Common Response Module (tCRM) score based on 11 genes (BASP1, ISG20, PSMB9, RUNX3, TAP1, NKG7, LCK, INPP5D, CXCL9, CD6, CXCL10; Khatri et al, 2013) which can diagnose the severity of tissue rejection, but this has not been validated in PT. In this study, we aimed to evaluate the locked tCRM score and identify additional markers of PT-AR. Materials and Methods: We performed a retrospective study applying gene expression analysis to RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 51 pancreas biopsies, grouped by histopathologic grade of acute cellular rejection (Grade 1 (n=14), Grade 2 (n=14), and Grade 3 (n=9)) versus normal (n=14). Gene expression analysis was performed using the Nanostring Cancer Immune v1.1 oligonucleotide set, which includes 40 set housekeeping (HK) genes. Appropriate HK genes were selected, data was log transformed and normalized. Differential gene expression (DE) analysis involved a negative binomial model, unsupervised hierarchical clustering, and calculation of the tCRM score with removal of Nanostring designated HK genes confounded by rejection. P-value was considered significant at <0.05 (Benjamini-Yekutieli, Mann-Whitney, Graph-Pad PRISM). Pathway analysis (PA) was performed to evaluate biological significance. Results: Some Nanostring designated HK genes showed significant differences with AR and hence a custom set of HK genes was used for normalization of log transformed data. Significant transcriptional differences were seen with higher grades of rejection in PT (Fig.1). The tCRM score, run on a sub-component of 11 genes, captures the same message with a scaled score that increases across rejection grades (Fig.2). Of the 22 genes differentially expressed in Grade 3, 18 were also significant in Grade 2. Specifically, within the 11 tCRM genes diagnostic of rejection in other solid organ transplants, 9 of 11 were significant for PT rejection, with the last two tCRM gene (CXCL9 and CXCL10) approaching significance at p=0.055 and 0.08 respectively. Conclusion: This study shows that a common hub of immune mediated genes, highly significant in transplant rejection (tCRM), and not confounded by tissue source (kidney, heart, liver and lung), were also highly informative for diagnosis and quantification of AR injury in PT. The bulk of the AR signal in PT, similar to other solid organs, is attributable to infiltration of activated leukocytes in the tissue, with background tissue injury specific transcriptional changes. The clinical and molecular drivers for Grade 1 PT rejection deserve additional analysis.Fig. 1.

Root transcriptome reveals efficient cell signaling and energy conservation key to aluminum toxicity tolerance in acidic soil adapted rice genotype

Aluminium (Al) toxicity is the single most important contributing factor constraining crop productivity in acidic soils. Hydroponics based screening of three rice genotypes, a tolerant (ARR09, AR), a susceptible (IR 1552, IR) and an acid soil adapted landrace (Theruvii, TH) revealed that AR accumulates less Al and shows minimum decrease in shoot and root biomass under Al toxicity conditions when compared with IR. Transcriptome data generated on roots (grown in presence or absence of Al) led to identification of ~1500 transcripts per genotype with percentage annotation ranging from 21.94% (AR) to 29.94% (TH). A total of 511, 804 and 912 DEGs were identified in genotypes AR, IR and TH, respectively. IR showed upregulation of transcripts involved in exergonic processes. AR appears to conserve energy by downregulating key genes of glycolysis pathway and maintaining transcript levels of key exergonic step enzymes under Al stress. The tolerance in AR appears to be as a result of novel mechanism as none of the reported Al toxicity genes or QTLs overlap with significant DEGs. Components of signal transduction and regulatory machinery like transcripts encoding zinc finger protein, calcieurin binding protein and cell wall associated transcripts are among the highly upregulated DEGs in AR, suggesting increased and better signal transduction in response to Al stress in tolerant rice. Sequencing of NRAT1 and glycine-rich protein A3 revealed distinct haplotype for indica type AR. The newly identified components of Al tolerance will help in designing molecular breeding tools to enhance rice productivity in acidic soils.

Signal Enhancement Strategies for Refractive Index-Sensitive Nanobiosensor.

Direct bio-monitoring essentially involves optical means since photon has insignificant effects over biomolecules. Over the years, laser induced surface Plasmon resonance method with various modifications as well as versatile localized Plasmon excited by incoherent light have facilitated in recording many nanobiological activities. Yet, monitoring interactions of small molecules including drugs requires signal amplification and improvement on signal-to-noise ratio. This paper focused on how the refractive index based nanobio-sensoring gold platform can produce more efficient, adaptable and more practical detection techniques to observe molecular interactions at high degree of sensitivity. It discusses surface chemistry approach, optimisation of the refractive index of gold platform and manipulation of gold geometry augmenting signal quality. In a normal-incidence reflectivity, r0 can be calculated using the Fresnel equation. Particularly at λ = 470 nm the ratio of r / r0 showed significant amplitude reduction mainly stemmed from the imaginary part of the Au refractive index. Hence, the fraction of reduction, Δr = 1 - r / r0. Experimentally, in a common reference frame reflectivity of a bare gold surface, R0 is compared with the reflectivity of gold surface in the presence of biolayer, R. The reduction rate (%) of reflectivity, ΔR = 1 - R / R0 is denoted as the AR signal. The method therefore enables quantitative measurement of the surface-bound protein by converting ΔR to the thickness, d, and subsequently the protein mass. We discussed four strategies to improve the AR signal by changing the effective refractive index of the biosensing platform. They are; a) Thickness optimisation of Au thin layer, b) Au / Ag bimetallic layer, c) composing alloy or Au composite, and d) Au thinlayer with nano or micro holes. As the result we successfully 'move' the refractive index, ε of the AR platform (gold only) to ε = -0.948 + 3.455i, a higher sensitivity platform. This was done by composing Au-Ag2O composite with ratio = 1:1. The results were compared to the potential sensitivity improvement of the AR substrate using other that could be done by further tailoring the ε advanced method. We suggested four strategies in order to realize this purpose. It is apparent that sensitivity has been improved through Au/Ag bimetallic layer or Au-Ag2O composite thin layer, This study is an important step towards fabrication of sensitive surface for detection of biomolecular interactions.

Abstract 705: Elucidating pediatric brain tumor pathophysiology by assessing signal transduction pathway activation

Abstract A major problem in pediatric neuro-oncology is lack of insight into underlying tumor biology, making treatment with targeted therapy challenging for this group of patients. To enable targeted therapy choice, understanding of underlying signal transduction pathway activity is required, as well as availability of appropriate diagnostic tests to predict therapy response. We have developed a novel method to identify activity of the ER, AR, HH, Wnt, TGFbeta, NFκB, and PI3K signal transduction pathways in an individual tissue sample. Our method is based on measuring mRNA levels of the pathway transcription factor target genes and interpreting these expression levels using a knowledge-based Bayesian network computational model which infers the probability of activity of the respective transcription factor (Verhaegh et al, Cancer Res. 2014). Public patient sample datasets from the GEO database were used to investigate pathway activation in pediatric brain tumors. In normal brain tissue from medulla, cerebellum, cerebral cortex and thalamus (GSE50161), pathway analysis showed no significant oncogenic pathway activation. Observed pathway activity in medulloblastoma was strongly correlated with known pathway-activating mutations, which was used as initial validation of these models for use in pediatric brain tumor diagnostics. In ependymoma (GSE66354), three distinct subtypes were analyzed: infratentorial posterior fossa A (PFA), PFB and supratentorial. These tumors are known to have a subtype-dependent prognosis; mainstay of therapy is surgery and radiation. Tumor driving pathway identification in pediatric ependymoma using mutation analysis is usually not helpful because epigenetic mechanisms prevail (Mack et al, Brain Pathology 2013). Using our pathway activity analysis, we find remarkable differences between different types of ependymoma with respect to signal transduction pathway activity. For PFA we find high NFκB and Wnt pathway activity. The dominant NFκB activity is in agreement with the described inflammatory phenotype. On the other hand, for PFB we find low NFκB and Wnt pathway activity. Finally, for supratentorial ependymoma we find almost all samples to have an active Hedgehog and Wnt pathway. We also analyzed multiple other pediatric tumors for pathway activity, for which data will be presented. The above pathway activity results provide highly interesting leads for targeted therapy selection, and we expect that such pathway analysis will have clinical utility in a neoadjuvant setting to reduce tumor size prior to surgery, and possibly also in an adjuvant setting to prevent recurrences. Citation Format: Laurent Holtzer, Wim Verhaegh, Anja Van de Stolpe. Elucidating pediatric brain tumor pathophysiology by assessing signal transduction pathway activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 705. doi:10.1158/1538-7445.AM2017-705

Order-of-magnitude differences in retention of low-energy Ar implanted in Si and SiO2

The retention of 1 and 5 keV Ar implanted at 45° in Si and 4.3 nm SiO2 on Si was studied at fluences between 3 × 1014 and 1.5 × 1016 cm−2. X-ray photoelectron spectroscopy (XPS) served to monitor the accumulation of Ar as well as the removal of SiO2. Bombardment induced changes in oxygen chemistry caused the O 1s peak position to move toward lower binding energies by as much as 2.2 eV. Plotted versus depth of erosion, the fluence dependent changes in oxygen content, and peak position were similar at 1 and 5 keV. The Ar content of Si increased with increasing exposure, saturating at fluences of ∼2 × 1015 cm−2 (1 keV) and ∼6 × 1015 cm−2 (5 keV). Much less Ar was retained in the SiO2/Si sample, notably at 1 keV, in which case the low-fluence Ar signal amounted to only 8% of the Si reference. The results imply that essentially no Ar was trapped in undamaged SiO2, i.e., the Ar atoms initially observed by XPS were located underneath the oxide. At the lowest fluence of 5 keV Ar, the retention ratio was much higher (43%) because the oxide was already highly damaged, with an associated loss of oxygen. The interpretation was assisted by TRIM(SRIM) calculations of damage production. Partial maloperation of the ion beam raster unit, identified only at a late stage of this work, enforced a study on the uniformity of bombardment. The desired information could be obtained by determining x,y line scan profiles of O 1s across partially eroded SiO2/Si samples. Fluence dependent Ar retention in Si was described using an extended version of the rapid relocation model which takes into account that insoluble implanted rare-gas atoms tend to migrate to the surface readily under ongoing bombardment. The range parameters required for the modeling were determined using TRIM(SRIM); sputtering yields were derived from the literature. The other three parameters determining the Ar signal, i.e., (1) the thickness w of the near-surface Si region devoid of Ar, (2) the relocation efficiency Ψrlc, and (3) the effective attenuation length L in XPS analysis were varied within reasonable limits until the calculated retention curves for 1 and 5 keV Ar in Si agreed with experimental data to better than 8%, using the same XPS sensitivity factor throughout. Results: w = 1.4 ± 0.1 nm, Ψrlc = 6.6 ± 0.5, and L = 2.7 ± 0.2 nm. Combining experimental and calculated data, it was found that the Ar trapping efficiency of the damaged oxide is intimately correlated with the loss of oxygen. The calculated stationary areal densities of all retained Ar are compared with results obtained by high-resolution medium-energy ion scattering spectrometry. Attractive areas of future research in rare gas retention and nanobubble formation are sketched briefly.

State Space Time Domain AR Signal Processing for Kalman Filter

Objective: Stochastic process have been performed useful in applications of signal and image processing in varied applications .Kalman filters are examples of such processing in state space time domain AR signals, AR process can be used as models of natural phenomena. Methods/Analysis: This paper explores the applications of Kalman filter AR signal processing using LMS in second algorithm, convergence speed is studied. RLS algorithm ensures fast convergences. Findings: Predictor - connector algorithm is used for mathematical modeling estimation of constant or random constant having process clatter in AR process has been done by discrete Kalman filter. It is formed that where covariance and dimensions clatter are invariable, the evaluation ever covariance and Kalman gain stabilized quickly. These limitations can be pre work out by running to filter off size. Novelty/Improvement: Estimation of true state by implement of discrete Kalman filter has shown that results are satisfied. Further extension can be done to estimate other stochastic parameters.

Atmospheric contamination of the primary Ne and Ar signal in mid-ocean ridge basalts and its implications for ocean crust formation

Both, terrestrial and extra-terrestrial applications of noble gases have demonstrated their importance as tracers for source identification, process characterisation and mass and heat flux quantification. However, the interpretation of noble gas isotope data from terrestrial igneous rocks is often complicated by the ubiquitous presence of heavy noble gases (Ne, Ar, Kr, Xe) with an atmospheric origin. Up to now there has been no consensus on how atmospheric noble gases are entrained into igneous rocks. Suggested processes range from contamination during sample preparation to mantle recycling through subduction. Here we present Ne, Ar, Mg, K, and Cl data of fresh glasses from the Mid-Atlantic Ridge north and south of the Ascension Fracture Zone which show that incorporation of atmospheric noble gases into igneous rocks is in general a two-step process: (1) magma contamination by assimilation of altered oceanic crust results in the entrainment of noble gases from air-equilibrated seawater; (2) atmospheric noble gases are adsorbed onto grain surfaces during sample preparation. This implies, considering the ubiquitous presence of the contamination signal, that magma contamination by assimilation of a seawater-sourced component is an integral part of mid-ocean ridge basalt evolution. Combining the results obtained from noble gas and Cl/K data with estimates of crystallisation pressures for the sample suite shows that the magma contamination must have taken place at a depth between 9 and 13km. Taking thickness estimates for the local oceanic crust into account, this implies that seawater penetration in this area reaches lower crustal levels, indicating that hydrothermal circulation might be an effective cooling mechanism even for the deep parts of the oceanic crust.

Effect of disease states on α1-adrenoceptor binding and signal transduction parameters in isolated perfused heart: quantification by pharmacokinetic-pharmacodynamic modelling

To employ a pharmacokinetic-pharmacodynamic modelling approach for analysing the effect of experimental endotoxemia and mild hypoxia on α1 -adrenoceptor (α1 AR) binding and signal transduction. In Langendorff-perfused rat hearts, phenylephrine was continuously infused, and [(3) H]-prazosin was injected as single dose (infused over 1 min). Simultaneous analysis of the time courses of prazosin outflow concentration and inotropic response (left ventricular developed pressure) using an agonist-antagonist interaction model and nonlinear regression allowed to estimate receptor affinity, as well as the parameters of the operational model of agonism. Both endotoxemia and hypoxia, significantly reduced the maximum response achievable in the system to 67% and 49% of the control group mean, respectively. In addition, endotoxemia decreased the efficiency of stimulus-response coupling and increased the steepness of the stimulus-response curve. In both disease models, no change in receptor affinity and density were found. The results revealed the causes of reduced α1 AR-mediated inotropic responsiveness in endotoxemia and hypoxia. In contrast with traditional dose-response studies, it was possible to quantify separately the underlying changes in α1 AR binding and signal transduction.

Testing for Nonlinearity Using Multi-dimensional Information Entropy

The choice of test statistics has a significant impact on the nonlinearity detection of time series. This paper proposes a new test statistic - multi-dimensional information entropy for the nonlinearity test. After applying IAAFT algorithm to create surrogate data, five test statistic methods, which include time reversibility, higher order autocovariance, nonlinear prediction error, approximate entropy and multi-dimensional information entropy, are employed to test the nonlinearity of AR signal, Henon signal, Lorenz signal, ECG signal and EDA signal. By comparing the test results, it indicates that the multidimensional information entropy is an effective and stable nonlinear test statistic. The multi-dimensional information entropy has high noise immunity and more sensitive to nonlinear signal.

Recent progress on nutraceutical research in prostate cancer

Recently, nutraceuticals have received increasing attention as the agents for cancer prevention and supplement with conventional therapy. Prostate cancer (PCa) is the most frequently diagnosed cancer and second leading cause of cancer-related death in men in the US. Growing evidences from epidemiological studies, in vitro experimental studies, animal studies, and clinical trials have shown that nutraceuticals could be very useful for the prevention and treatment of PCa. Several nutraceuticals including isoflavone, indole-3-carbinol, 3,3'-diindolylmethane, lycopene, (-)-epigallocatechin-3-gallate, and curcumin are known to downregulate the signal transductions in AR, Akt, NF-κB, and other signal transduction pathways which are vital for the development of PCa and the progression of PCa from androgen-sensitive to castrate-resistant PCa. Therefore, nutraceutical treatment in combination with conventional therapeutics could achieve better treatment outcome in prostate cancer therapy. Interestingly, some nutraceuticals could regulate the function of cancer stem cell (CSC)-related miRNAs and associated molecules, leading to the inhibition of prostatic CSCs which are responsible for drug resistance, tumor progression, and recurrence of PCa. Hence, nutraceuticals may serve as powerful agents for the prevention of PCa progression and they could also be useful in combination with chemotherapeutics or radiotherapy. Such strategy could become a promising newer approach for the treatment of metastatic PCa with better treatment outcome by improving overall survival.

AR model whitening and signal detection based on GLD algorithm in the non-Gaussian reverberation

The paper analyzes the characteristics of shallow sea reverberation such as divergent variance and heavy tails in probability density distribution and matches it to symmetric alpha stable (SαS) distribution. After analyzing the AR model whitening method based on Gaussian distribution and Levinson–Durbin algorithm, the paper proposes and derives the generalized Levinson–Durbin (GLD) algorithm based on covariation theory of alpha stable distribution. The GLD algorithm can estimate the order and parameters of AR SαS model by iterations which are fast and effective in calculating, and then the performance tests by simulations are given. The AR model whitening method using GLD algorithm has a faster speed and a better detection performance than AR Gaussian whitening method in impulsive reverberation. At last the Monte Carlo simulating tests are used to validate the validity of the new method.

Transmission electron microscopy study of Ar‐filled bubbles in steel

Ar-filled bubbles in an oxide-dispersion-strengthened (ODS) alloy were characterized by analytical transmission electron microscopy. Energy dispersive X-ray analysis combined with nanoscale imaging was employed for quantitative analysis of Ar gas locked in a bubble 6 nm in size. As the Ar bubbles are formed at the ODS particles - matrix interface, the known Ti(2)Y(2)O(7) composition and size of ODS particles served as a reference in quantification of the Ar signal and for the calculation of the bubble size and the Ar density inside. The Ar pressure was also calculated by modified Van der Waals equation.

On the ionic chemistry in DC cold plasmas of H2 with Ar

An experimental diagnosis and kinetic modeling of the ionic chemistry in low pressure DC plasmas of H(2)/Ar has been carried out. The studies were performed at pressures of 2 Pa and 0.7 Pa, in a hollow-cathode discharge reactor, using as plasma precursor a H(2)/Ar mixture with 15% Ar content. Experimental measurements include distributions of ion fluxes to the cathode, as well as electronic temperatures and densities in the plasma glow. Besides the species resulting directly from electron impact ionization (H(+), H(2)(+), Ar(+) and Ar(2+)), the ions H(3)(+) and ArH(+) were found to be formed in large amounts through protonation reactions in the glow. In spite of the not too large variation in the pressure of the two plasmas, the differences in the ion distributions are worth mentioning. In the 2 Pa discharge (but not in the 0.7 Pa), H(3)(+) was the dominant ion and ArH(+) exceeded markedly the Ar(+) signal. On the other hand, the appearance of Ar(2+) in the two plasmas points at the relevance of high energy electrons. The experimental results can be accounted for by a simple kinetic model, after including corrections for the presence of a small fraction (<3%) of high energy (>50 eV) electrons and for the attenuation of the Ar(+) ions in the sheath through asymmetric charge exchange with H(2).

Facilitatory Interplay in α1aand β2Adrenoceptor Function Reveals a Non-GqSignaling Mode: Implications for Diversification of Intracellular Signal Transduction

Agonist occupied alpha(1)-adrenoceptors (alpha(1)-ARs) engage several signaling pathways, including phosphatidylinositol hydrolysis, calcium mobilization, arachidonic acid release, mitogen-activated protein (MAP) kinase activation, and cAMP accumulation. The natural agonist norepinephrine (NE) activates with variable affinity and intrinsic efficacy all adrenoceptors, and in cells that coexpress alpha(1)- and beta-AR subtypes, such as cardiomyocytes, this leads to coactivation of multiple downstream pathways. This may result in pathway cross-talk with significant consequences to heart physiology and pathologic state. To dissect signaling components involved specifically in alpha(1A)- and beta(2)-AR signal interplay, we have developed a recombinant model system that mimics the levels of receptor expression observed in native cells. We followed intracellular Ca(2+) mobilization to monitor in real time the activation of both G(q) and G(s) pathways. We found that coactivation of alpha(1A)- and beta(2)-AR by the nonselective agonist NE or via a combination of the highly selective alpha(1A)-AR agonist A61603 and the beta-selective agonist isoproterenol led to increases in Ca(2+) influx from the extracellular compartment relative to stimulation with A61603 alone, with no effect on the associated transient release of Ca(2+) from intracellular stores. This effect became more evident upon examination of an alpha(1A)-AR variant exhibiting a partial defect in coupling to G(q), and we attribute it to potentiation of a non G(q)-pathway, uncovered by application of a combination of xestospongin C, an endoplasmic reticulum inositol 1,4,5-triphosphate receptor blocker, and 2-aminoethoxydiphenyl borate, a nonselective storeoperated Ca(2+) entry channel blocker. We also found that stimulation with A61603 of a second alpha(1A)-AR variant entirely unable to signal induced no Ca(2+) unless beta(2)-AR was concomitantly activated. These results may be accounted for by the presence of alpha(1A)/beta(2)-AR heterodimers or alternatively by specific adrenoceptor signal cross-talk resulting in distinct pharmacological behavior. Finally, our findings provide a new conceptual framework to rationalize outcomes from clinical studies targeting alpha- and beta-adrenoceptors.

Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction: Evidence of improved vascular α 1-adrenoreceptor signal transduction

Alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation produces smooth muscle contraction, vasoconstriction, and myocyte hypertrophy, suggesting a potential therapeutic role for alpha(1)-AR antagonists to reduce cardiac workload and myocardial hypertrophy. Preliminary reports suggest that vascular alpha(1)-ARs are desensitized in heart failure (HF) in a manner similar to myocardial beta(1)-ARs. We examined alpha(1)-AR signal transduction by repeat phenylephrine (PE) infusions in patients with HF receiving chronic carvedilol therapy. Twelve subjects with HF not currently receiving beta-blockers were up-titrated to maximum tolerable doses of carvedilol. Subjects underwent alpha(1)-AR stimulation testing at study baseline, 2 weeks after each dose titration, and 6 months after maintenance of maximum carvedilol dose. Phenylephrine infusions began at 0.5 microg kg(-1) min(-1), with dose titrations every 10 minutes, to a maximum of 5 microg kg(-1) min(-1). Phenylephrine dose response was evaluated by the PE rate required to elicit a 20 mm Hg increase in systolic blood pressure (BP), designated PS(20). All doses of carvedilol significantly reduced preinfusion measures of heart rate, systolic BP, diastolic BP, and mean arterial pressure. However, carvedilol also produced a paradoxical trend toward PS(20) reduction (indicating increased PE response) that reached significance at the completion of carvedilol dose titration (PS(20) ratio vs baseline = 0.78; P < .001). All effects were maintained over a 6-month treatment period with no evidence of tolerance. Increasing BP response to PE infusion suggests improvement in vascular alpha(1)-AR signal transduction with chronic carvedilol therapy. This effect is evident despite no detectable tolerance to preinfusion BP reductions. The varying affinities of alpha(1)-AR subtypes for carvedilol and PE may have contributed to this finding.

Distributed Detection in Wireless Sensor Networks Using A Multiple Access Channel

Distributed detection in a one-dimensional (1-D) sensor network with correlated sensor observations, as exemplified by two problems-detection of a deterministic signal in correlated Gaussian noise and detection of a first-order autoregressive [AR(1)] signal in independent Gaussian noise, is studied in this paper. In contrast with the traditional approach where a bank of dedicated parallel access channels (PAC) is used for transmitting the sensor observations to the fusion center, we explore the possibility of employing a shared multiple access channel (MAC), which significantly reduces the bandwidth requirement or detection delay. We assume that local observations are mapped according to a certain function subject to a power constraint. Using the large deviation approach, we demonstrate that for the deterministic signal in correlated noise problem, with a specially chosen mapping rule, MAC fusion achieves the same asymptotic performance as centralized detection under the average power constraint (APC), while there is always a loss in error exponents associated with PAC fusion. Under the total power constraint (TPC), MAC fusion still results in exponential decay in error exponents with the number of sensors, while PAC fusion does not. For the AR signal problem, we propose a suboptimal MAC mapping rule which performs closely to centralized detection for weakly correlated signals at almost all signal-to-noise ratio (SNR) values, and for heavily correlated signals when SNR is either high or low. Finally, we show that although the lack of MAC synchronization always causes a degradation in error exponents, such degradation is negligible when the phase mismatch among sensors is sufficiently small

Radio frequency glow discharge optical emission spectrometry (rf-GD-OES) analysis of solid glass samples

The analytical characteristics of rf-GD-OES for the elemental analysis of bulk solid glass specimens are investigated. Studies are carried out to evaluate the role of the major operating parameters—discharge power and pressure, use of an external argon (bath) gas, sample thickness, and internal standard normalization. Plasma stabilization and signal response are optimized at 30 W rf power and 6 Torr as suggested by the relative standard deviation of the background (RSDB) and signal to background ratio (S/B) values respectively. Basic figures of merit are further improved with the introduction of the argon (bath) gas, decreasing by a minimum of 25% of the original %RSD values of the sample-to-sample S/B ratios. Variations in analyte signal intensities due to differences in sample thickness are quantitatively corrected using internal standard (normalization) based on the relative response of the Ar(I) optical emission. Limits of detection (LOD) are on the single µg g−1 level, which are comparable to some other OES methods. Linear calibration curves over the range of ∼1–500 ppm are obtained using the Ar(I) signal emission as the normalizing internal standard.

Calibration of pressure‐dependent sensitivity and discrimination in Nier‐type noble gas ion sources

The efficiency of many noble gas mass spectrometers to ionize gas species is known to be a function of the pressure of gas in the spectrometer. This work shows how the half plate voltage for maximum He or Ar signal depends on the spectrometer pressure and shows that the half plate voltage for maximum 4He sensitivity does not coincide with the half plate voltage for maximum 3He sensitivity. In addition, half plate voltage has a greater control on sensitivity at higher spectrometer pressures. Variations in He and Ar sensitivity and isotopic discrimination as a function of pressure are due, at least in part, to these variations in the position of maximum sensitivity with respect to half plate voltage. The maximum sensitivity settings shift to lower half plate voltage at high spectrometer pressures, irrespective of if the pressure increase is due to the gas being investigated or a different species. Therefore noble gas mass spectrometers should always be tuned at the maximum possible pressure; measurements at higher pressures should be avoided. Significant errors in the spectrometer sensitivity and discrimination can result from improper tuning and calibration of noble gas mass spectrometers.