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

Phase Diagram of Pressure-Induced Superconductivity in EuFe2As2 Probed by High-Pressure Resistivity up to 3.2 GPa

We have constructed a pressure$-$temperature ($P-T$) phase diagram of $P$-induced superconductivity in EuFe$_2$As$_2$ single crystals, via resistivity ($\rho$) measurements up to 3.2 GPa. As hydrostatic pressure is applied, an antiferromagnetic (AF) transition attributed to the FeAs layers at $T_\mathrm{0}$ shifts to lower temperatures, and the corresponding resistive anomaly becomes undetectable for $P$ $\ge$ 2.5 GPa. This suggests that the critical pressure $P_\mathrm{c}$ where $T_\mathrm{0}$ becomes zero is about 2.5 GPa. We have found that the AF order of the Eu$^{2+}$ moments survives up to 3.2 GPa without significant changes in the AF ordering temperature $T_\mathrm{N}$. The superconducting (SC) ground state with a sharp transition to zero resistivity at $T_\mathrm{c}$ $\sim$ 30 K, indicative of bulk superconductivity, emerges in a pressure range from $P_\mathrm{c}$ $\sim$ 2.5 GPa to $\sim$ 3.0 GPa. At pressures close to but outside the SC phase, the $\rho(T)$ curve shows a partial SC transition (i.e., zero resistivity is not attained) followed by a reentrant-like hump at approximately $T_\mathrm{N}$ with decreasing temperature. When nonhydrostatic pressure with a uniaxial-like strain component is applied using a solid pressure medium, the partial superconductivity is continuously observed in a wide pressure range from 1.1 GPa to 3.2 GPa.Comment: 7 pages, 6 figures, accepted for publication in Physical Review B, selected as "Editors' Suggestion

Proximal nested sampling with data-driven priors for physical scientists

Proximal nested sampling was introduced recently to open up Bayesian model selection for high-dimensional problems such as computational imaging. The framework is suitable for models with a log-convex likelihood, which are ubiquitous in the imaging sciences. The purpose of this article is two-fold. First, we review proximal nested sampling in a pedagogical manner in an attempt to elucidate the framework for physical scientists. Second, we show how proximal nested sampling can be extended in an empirical Bayes setting to support data-driven priors, such as deep neural networks learned from training data.Comment: 9 pages, 4 figure

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

A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for {beta} subunit interaction

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel {alpha} subunit. The mutation decreased modulation of the {alpha} subunit by {beta}1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of {beta}1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type{alpha} subunit with the {beta}1or {beta}3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for {beta} subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the {alpha} and {beta}1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility

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