Agonist-Specific Calcium Signaling and Phosphoinositide Hydrolysis in Human SK-N-MCIXC Neuroepithelioma Cells

Fura-2 digital imaging microfluorimetry was used to evaluate the Ca 2+ signals generated in single clonal human neuroepithelioma cells (SK-N-MCIXC) in response to agonists that stimulate phosphoinositide hydrolysis. Addition of optimal concentrations of either endothelin-1 (ET-1), ATP, oxotremorine-M (Oxo-M), or norepinephrine (NE) all resulted in an increase in the concentration of cytosolic calcium (Ca 2+ i ) but of different magnitudes (ET-1 = ATP> NE). The Ca 2+ signals elicited by the individual agonists also differed from each other in terms of their latency of onset, rate of rise and decay, and prevalence of a sustained phase of Ca 2+ influx. The Ca 2+ signals that occurred in response to ATP had a shorter latency and more rapid rates of rise and decay than those observed for the other three agonists. Furthermore, a sustained plateau phase of the Ca 2+ signal, which was characteristic of the response to Oxo-M, was observed in 94% of cells responded to ET-1 or ATP, whereas corresponding values for Oxo-M and NE were ∼74 and ∼48%. Sequential addition of agonists to cells maintained in a Ca 2+ -free buffer indicated that each ligand mobilized Ca 2+ from a common intracellular pool. When monitored as a release of a total inositol phosphate fraction, all four agonists elicited similar (four- to sixfold) increases in phosphoinositide hydrolysis. However, the addition of ET-1 or ATP resulted in larger increases in the net formation of inositol 1,4,5-trisphosphate than did either Oxo-M or NE. These results indicate that, in SK-N-MCIXC cells, the characteristics of both Ca 2+ signaling and inositol phosphate production are agonist specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66414/1/j.1471-4159.1994.63062099.x.pd

Design and Vertical Tests of SPS-series Double-Quarter Wave (DQW) Cavity Prototypes for the HL-LHC Crab Cavity System

Crab crossing is essential for high-luminosity colliders. The High Luminosity Large Hadron Collider (HL-LHC) will equip one of its Interaction Points (IP1) with Double-Quarter Wave (DQW) crab cavities. A DQW cavity is a new generation of deflecting RF cavities that stands out for its compactness and broad frequency separation between fundamental and first high-order modes. The deflecting kick is provided by its fundamental mode. Each HL-LHC DQW cavity shall provide a nominal deflecting voltage of 3.4 MV, although up to 5.0 MV may be required. A Proof-of-Principle (PoP) DQW cavity was limited by quench at 4.6 MV. This paper describes a new, highly optimized cavity, designated DQW SPS-series, which satisfies dimensional, cryogenic, manufacturing and impedance requirements for beam tests at SPS and operation in LHC. Two prototypes of this DQW SPS-series were fabricated by US industry and cold tested after following conventional SRF surface treatment. Both units outperformed the PoP cavity, reaching a deflecting voltage of 5.3-5.9 MV. This voltage - the highest reached by a DQW cavity - is well beyond the nominal voltage of 3.4 MV and may even operate at the ultimate voltage of 5.0MVwith sufficient margin. This paper covers fabrication, surface preparation and cryogenic RF test results and implications

Galileo dust data from the jovian system: 2000 to 2003

The Galileo spacecraft was orbiting Jupiter between Dec 1995 and Sep 2003. The Galileo dust detector monitored the jovian dust environment between about 2 and 370 R_J (jovian radius R_J = 71492 km). We present data from the Galileo dust instrument for the period January 2000 to September 2003. We report on the data of 5389 particles measured between 2000 and the end of the mission in 2003. The majority of the 21250 particles for which the full set of measured impact parameters (impact time, impact direction, charge rise times, charge amplitudes, etc.) was transmitted to Earth were tiny grains (about 10 nm in radius), most of them originating from Jupiter's innermost Galilean moon Io. Their impact rates frequently exceeded 10 min^-1. Surprisingly large impact rates up to 100 min^-1 occurred in Aug/Sep 2000 when Galileo was at about 280 R_J from Jupiter. This peak in dust emission appears to coincide with strong changes in the release of neutral gas from the Io torus. Strong variability in the Io dust flux was measured on timescales of days to weeks, indicating large variations in the dust release from Io or the Io torus or both on such short timescales. Galileo has detected a large number of bigger micron-sized particles mostly in the region between the Galilean moons. A surprisingly large number of such bigger grains was measured in March 2003 within a 4-day interval when Galileo was outside Jupiter's magnetosphere at approximately 350 R_J jovicentric distance. Two passages of Jupiter's gossamer rings in 2002 and 2003 provided the first actual comparison of in-situ dust data from a planetary ring with the results inferred from inverting optical images.Comment: 59 pages, 13 figures, 6 tables, submitted to Planetary and Space Scienc

Genome size and ploidy of Paracoccidioides brasiliensis reveals a haploid DNA content: Flow cytometry and GP43 sequence analysis

The aim of this study was to evaluate genome size and ploidy of the dimorphic pathogenic fungus Paracoccidioides brasiliensis. The cell cycle analysis of 10 P. brasiliensis isolates by flow cytometry (FCM) revealed a genome size ranging from 26.3+/-0.1Mb (26.9+/-0.1fg) to 35.5+/-0.2Mb (36.3+/-0.2fg) per uninucleated yeast cell. The DNA content of conidia from P. brasiliensis ATCC 60855-30.2+/-0.8Mb (30.9+/-0.8fg) -showed no significant differences with the yeast form, possibly excluding the occurrence of ploidy shift during morphogenesis. The ploidy of several P. brasiliensis isolates was assessed by comparing genome sizing by FCM with the previously described average haploid size obtained from electrophoretic karyotyping. The analysis of intra-individual variability of a highly polymorphic P. brasiliensis gene, GP43, indicated that only one allele seems to be present. Overall, the results showed that all analysed isolates presented a haploid, or at least aneuploid, DNA content and no association was detected between genome size/ploidy and the clinical-epidemiological features of the studied isolates. This work provides new knowledge on P. brasiliensis genetics/genomics, important for future research in basic cellular/molecular mechanisms and for the development/design of molecular techniques in this fungus

Understanding the WMAP Cold Spot mystery

The first and third year data releases from the WMAP provide evidence of an anomalous Cold Spot (CS) at galactic latitude b=-57deg and longitude l=209deg. We have examined the properties of the CS in some detail in order to assess its cosmological significance. We have performed a cluster analysis of the local extrema in the CMB signal to show that the CS is actually associated with a large group of extrema rather than just one. In the light of this we have re-examined the properties of the WMAP ILC and co-added "cleaned" WCM maps, which have previously been used for the analysis of the properties of the signal in the vicinity of the CS. These two maps have remarkably similar properties on equal latitude rings for |b|>30deg, as well as in the vicinity of the CS. We have also checked the idea that the CMB signal has a non-Gaussian tail, localized in the low multipole components of the signal. For each ring we apply a linear filter with characteristic scale R, dividing the CMB signal in two parts: the filtered part, with characteristic scale above that of the filter R, and the difference between the initial and filtered signal. Using the filter scale as a variable, we can maximize the skewness and kurtosis of the smoothed signal and minimize these statistics for the difference between initial and filtered signal. We have discovered that the shape of the CS is formed primarily by the components of the CMB signal represented by multipoles between 10<=L<=20, with a corresponding angular scale about 5-10 degs. This signal leads to modulation of the whole CMB sky, clearly seen at |b|>30deg in both the ILC and WCM maps, rather than a single localized feature. After subtraction of this modulation, the remaining part of the CMB signal appears to be consistent with statistical homogeneity and Gaussianity.Comment: 35 pages, 17 figure

General practitioners' beliefs about effectiveness and intentions to prescribe smoking cessation medications: qualitative and quantitative studies

BACKGROUND: General practitioners' (GPs) negative beliefs about nicotine dependence medications may act as barriers to prescribing them. METHODS: Study1: Twenty-five GPs from 16 practices across London were interviewed in this qualitative study. Framework analysis was used to identify key themes. Study 2: A convenience sample of 367 GPs completed an internet-based survey. Path-analysis was used to examine the relations between beliefs and intentions to prescribe smoking cessation medications. RESULTS: Study 1: Whilst nicotine replacement therapy (NRT) and bupropion were generally perceived as effective and cost-effective, the effectiveness of NRT was seen as critically dependent on behavioural support for smoking cessation. This dependence appeared to be influenced by perceptions that without support smokers would neglect psychological aspects of smoking and use NRT incorrectly. GPs perceived bupropion as dangerous and were concerned about its side-effects. Study 2: GPs' beliefs had medium (NRT, f(2 )= .23) to large (bupropion, f(2)=.45; NRT without support, f(2)=.59) effects on their intentions to prescribe medications. Beliefs about effectiveness of NRT and bupropion and the perceived danger of bupropion were the key predictors of intentions to prescribe NRT and bupropion, respectively. Beliefs about neglecting psychological aspects of smoking and incorrect use had indirect effects on intentions to prescribe NRT without support, operating via beliefs about effectiveness. CONCLUSION: GPs vary in their beliefs about the effectiveness and safety of smoking cessation medications. Their intentions to prescribe these medications vary in line with these beliefs. Interventions aimed at increasing the likelihood with which GPs prescribe these medications may be more effective if they addressed these beliefs

Unusual behaviors in the transport properties of REFe4_{4}P12_{12} (RE: La, Ce, Pr, and Nd)

We have investigated the resistivity ($\rho$), thermoelectric power (TEP) and Hall coefficient ($R_{H}$) on high quality single crystals of REFe$_{4}$P$_{12}$. TEP in CeFe$_{4}$P$_{12}$ is extremely large ($\sim$ 0.5mV/K at 290K) with a peak of $\sim$ 0.75mV/K at around 65K. The Hall mobility also shows a peak at $\sim$ 65K, suggesting carriers with heavy masses developed at lower temperatures related with the f-hybridized band. Both Pr- and Nd- systems exhibit an apparent increase of $\rho$ with decreasing temperature far above their magnetic transition temperatures. In the same temperature ranges, TEP exhibits unusually large absolute values of -50$\mu$V/K for PrFe$_{4}$P$_{12}$ and -15$\mu$V/K for NdFe$_{4}$P$_{12}$, respectively. For PrFe$_{4}$P$_{12}$, such anomalous transport properties suggest an unusual ground state, possibly related with the Quadrupolar Kondo effect.Comment: 5 pages, 8 figure