julilili42/papers huggingface dataset:
Pharmacological Activation of Normal and Arrhythmia-Associated Mutant KCNQ1 Potassium Channels
2003-10-28

KCNQ1 α-subunits coassemble with KCNE1 β-subunits to form channels that conduct the slow delayed rectifier K + current ( I Ks ) important for repolarization of the cardiac action potential. Mutations in KCNQ1 reduce I Ks and cause long-QT syndrome, a disorder of ventricular repolarization that predisposes affected individuals to arrhythmia and sudden death. Current therapy for long-QT syndrome is inadequate. R-L3 is a benzodiazepine that activates I Ks and has the potential to provide gene-specific therapy. In the present study, we characterize the molecular determinants of R-L3 interaction with KCNQ1 channels, use computer modeling to propose a mechanism for drug-induced changes in channel gating, and determine its effect on several long-QT syndrome–associated mutant KCNQ1 channels heterologously expressed in Xenopus oocytes. Scanning mutagenesis combined with voltage-clamp analysis indicated that R-L3 interacts with specific residues located in the 5th and 6th transmembrane domains of KCNQ1 subunits. Most KCNQ1 mutant channels responded to R-L3 similarly to wild-type channels, but one mutant channel (G306R) was insensitive to R-L3 possibly because it disrupted a key component of the drug-binding site.
INTEGRAL Spectrometer SPI's GRB detection capabilities
2003-10-28

The spectrometer SPI, one of the two main instruments of the INTEGRAL spacecraft, offers significant gamma-ray burst detection capabilities. In its 35° (full width) field of view SPI is able to localise gamma-ray bursts at a mean rate of ~0.8/month. With its large anticoincidence shield of 512 kg of BGO crystals SPI is able to detect gamma-ray bursts quasi omni-directionally with a very high sensitivity. Burst alerts of the anticoincidence shield are distributed by the INTEGRAL Burst Alert System. In the first 8 months of the mission about 0.8/day gamma-ray burst candidates and 0.3/day gamma-ray burst positions were obtained with the anticoincidence shield by interplanetary network triangulations with other spacecrafts.
Surfactant in Newborn Compared with Adolescent Pigs
2003-10-28

Surfactant composition and function differ between vertebrates, depending on pulmonary anatomy and respiratory physiology. Because pulmonary development in pigs is similar to that in humans, we investigated surface tension function, composition of phospholipid molecular species, and concentrations of surfactant protein (SP)-A to -D in term newborn pigs (NP) compared with adolescent pigs (AP), using the pulsating bubble surfactometer, mass spectrometry, high-performance liquid chromatography, and immunoblot techniques (IT). NP was more potent than AP surfactant in reaching minimal surface tension values near zero mN/m. Whereas SP-A and SP-D were comparable, SP-B and SP-C were increased 3- to 4-fold in NP surfactant. Moreover, fluidizing phospholipids such as palmitoylmyristoyl-PC (PC16:0/14:0) and palmitoylpalmitoleoyl-PC (PC16:0/16:1) were increased at the expense of PC16:0/16:0 (32.4 +/- 0.6 versus 44.5 +/- 3.2%, respectively). Whereas concentrations of total anionic phospholipids were similar in NP and AP surfactant (9.9 +/- 0.3 and 12.0 +/- 0.3%, respectively), phosphatidylinositol was the predominant anionic phospholipid in NP surfactant. We conclude that, compared with AP, NP surfactant displays better surface tension function under dynamic conditions, which is associated with increased concentrations of SP-B and SP-C, as well as fluidizing phospholipids at the expense of PC16:0/16:0.
Simultaneous observations of the quasar 3C 273 with INTEGRAL, XMM-Newton and RXTE
2003-10-28

INTEGRAL has observed the bright quasar 3C 273 on 3 epochs in January 2003 as one of the first observations of the open programme. The observation on January 5 was simultaneous with RXTE and XMM-Newton observations. We present here a first analysis of the continuum emission as observed by these 3 satellites in the band from 3 keV to 500 keV. The continuum spectral energy distribution of 3C 273 was observed to be weak and steep in the high energies during this campaign. We present the actual status of the cross calibrations between the instruments on the three platforms using the calibrations available in June 2003.
SPI-specific analysis method and software overview
2003-10-28

The SPI spectrometer on INTEGRAL features a camera system with 19 Ge detector modules, imaging photons through a tungsten coded mask. Background is reduced by an anticoincidence detector system surrounding these. The specifics of this instrument lead to data correction and analysis methods which are described here. Raw data for science analysis are detector event messages and spectra for different categories of detector hits and pulse shapes. Preprocessing combines calibrated spectra from these, which are then interpreted using the imaging and spectral response function for measured spectra where parts of the detector plane are occulted by the mask. Background dominates the overall signal, tailored background estimates and models are based on instrument-specific signatures, their correlations, and trends.
FirstINTEGRALobservations of Cygnus X-3
2003-10-28

We present the first INTEGRAL results on Cyg X-3 from the PV phase observations of the Cygnus region. The source was clearly detected by the JEM-X, ISGRI and SPI detectors. The INTEGRAL observations were supported by simultaneous pointed RXTE observations. Their lightcurves folded over the 4.8 hour binary period are compatible with the mean RXTE/ASM and CGRO/BATSE light curves. We fit our broad band X-ray/Gamma-ray spectra with a physical model, which represents the first such published model for Cyg X-3. The main physical processes in the source are thermal Comptonization and Compton reflection with parameters similar to those found for black-hole binaries at high Eddington rates.
First results from the INTEGRAL galactic plane scans
2003-10-28

\\n Scans of the Galactic plane performed \\n at regular intervals constitute a key element of the guaranteed time \\n observations of the INTEGRAL \\n observing programme. These scans are done for two reasons: frequent\\n monitoring of the Galactic plane in order to detect transient sources, and\\n time resolved mapping of the Galactic plane in continuum and diffuse line\\n emission. This paper describes first results obtained from the Galactic\\n plane scans executed so far during the early phase (Dec. 2002–May 2003) of the nominal mission.\\n \\n \\n
INTEGRAL results on GRB 030320: A long gamma-ray burst detected at the edge of the field of view
2003-10-28

\\n GRB 030320 is the 5th gamma-ray burst (GRB) detected by INTEGRAL in the field of view (FoV). \\nIt is so far the GRB with the largest off-axis angle with respect to the INTEGRAL pointing direction, \\nnear to the edge of the FoV of both main instruments, IBIS and\\nSPI. Nevertheless, it was possible to determine its position and to extract spectra and fluxes. \\nThe GRB nature of the event was confirmed by an IPN triangulation. \\nIt is a ~60 s long GRB with two prominent peaks\\nseparated by ~35 s. The spectral shape of the GRB is best\\nrepresented by a single power law with a photon index . The\\npeak flux in the 20–200 keV band is determined to ~5.7 photons cm-2 s-1 \\nand the GRB fluence to erg cm-2. \\nAnalysing the spectral evolution of the GRB, a “hard-to-soft” behaviour emerges. \\nA search for an optical counterpart has been carried out, but none was found.\\n \\n \\n
GRB 021125: The first GRB imaged by INTEGRAL
2003-10-28

\\n In the late afternoon of November 25th, \\n2002 a gamma–ray burst (GRB) was detected in the partially coded field\\nof view (about from the centre)\\nof the imager IBIS on board the INTEGRAL satellite.\\nThe instruments on-board INTEGRAL allowed, for the first time, the observation of the prompt gamma-ray emission over a broad energy band from 15 to 500 keV.\\nGRB 021125 lasted ~24 s with a mean flux of ~5.0 photons cm-2 s-1 in the 20–500 keV energy band, and a fluence of\\n~ erg cm-2 in the same energy band.\\nHere we report the analysis of the data from the imager IBIS\\nand the spectrometer SPI. \\n \\n
Time resolved spectroscopy of GRB 030501 using INTEGRAL
2003-10-28

The gamma-ray instruments on-board INTEGRAL offer an unique opportunity to perform time resolved analysis on GRBs. The imager IBIS allows accurate positioning of GRBs and broad band spectral analysis, while SPI provides high resolution spectroscopy. GRB 030501 was discovered by the INTEGRAL Burst Alert System in the ISGRI field of view. Although the burst was fairly weak (fluence <em>F</em><sub>20-200keV</sub> ≃ 3.5 × 10<sup>-6</sup> erg cm<sup>-2</sup>) it was possible to perform time resolved spectroscopy with a resolution of a few seconds. The GRB shows a spectrum in the 20-400 keV range which is consistent with a spectral index Γ = -1.8. No emission line or spectral break was detectable in the spectrum. Although the flux seems to be correlated with the hardness of the GRB spectrum, there is no clear soft to hard evolution seen over the duration of the burst. The INTEGRAL data have been compared with results from the Ulysses and RHESSI experiments.
GRB 021219: The first Gamma-Ray Burst localized in real time with IBAS
2003-10-28

\\n \\nOn December 19, 2002, during the Performance and Verification Phase of INTEGRAL,\\na Gamma-Ray Burst (GRB) has been detected and localized in real time\\nwith the INTEGRAL Burst Alert System (IBAS). Here we present the results\\nobtained with the IBIS and SPI instruments.\\nThe burst had a time profile with a single peak lasting about 6 s.\\nThe peak spectrum can be described by a single power law with photon\\nindex and\\nflux ~3.7 photons cm-2 s-1 (20–200 keV).\\nThe fluence in the same energy range is\\n erg cm-2.\\nTime resolved spectroscopy performed with IBIS/ISGRI shows\\na clear hard to soft evolution of the spectrum.\\n\\n\\n
Observation of Lasing Mediated by Collective Atomic Recoil
2003-10-29

We observe the buildup of a frequency-shifted reverse light field in a unidirectionally pumped high-Q optical ring cavity serving as a dipole trap for cold atoms. This effect is enhanced and a steady state is reached, if via an optical molasses an additional friction force is applied to the atoms. We observe the displacement of the atoms accelerated by momentum transfer in the backscattering process and interpret our observations in terms of the collective atomic recoil laser. Numerical simulations are in good agreement with the experimental results.
Transmission electron microscopic observations of membrane effects of antibiotic cecropin B on Escherichia coli
2003-10-29

Abstract The pathway of cell membrane lysis by the peptide antibiotic cecropin B (CB), which contains both a hydrophobic and an amphipathic α‐helix, was analysed by assessing the morphological changes of Escherichia coli following treatment with the peptide. Exposure of green fluorescent protein (GFP)‐expressing E. coli to CB does not lead to an efflux of GFP. Moreover, transmission electron microscopic (TEM) examination of cecropin B‐treated cells showed that severe swelling precedes cell death and that the outer membrane becomes distended away from the plasma membrane. Using immuno‐gold staining and TEM of E. coli expressing the maltose‐binding protein in the cytoplasm, it was apparent that the protein remains restricted to the cytoplasmic compartment. These observations suggest that CB causes gross disruption of the outer membrane of Gram‐negative bacteria. Circular dichroism measurements of CB in the presence of cell membrane‐mimicking liposomes showed that CB forms secondary structure dependent on the ratio of [lipid]/[peptide]. These observations from this study are important for the future design of custom antimicrobial peptides. Microsc. Res. Tech. 62:423–430, 2003. © 2003 Wiley‐Liss, Inc.
Magnetic interaction parameters from paramagnetic diffuse neutron scattering in MnO
2003-10-29

Magnetic interaction parameters are generally determined from magnon dispersion curves obtained by neutron inelastic-scattering experiments in the ordered phase at low temperature. At higher temperature, above the phase transition, the parameters have to be extracted from the diffuse scattering distribution. Using a mean field theory extended by an Onsager reaction term we demonstrate that the interactions can also be determined in the paramagnetic phase. The theory describes well the paramagnetic phase of MnO in a large temperature range from 130 to 220 K.
On the competitive growth of two sand heaps
2003-10-29

Abstract A simple quasistationary model for the growth of 1D sand heaps in form of a non‐linear system of ordinary differential equations is presented. The basic assumption for the model is the instantaneous deposition of the matter which is poured by punctiform sources. Existence and uniqueness of the solution is shown, and the qualitative evolution, especially the overrun phenomenon, is described. Copyright © 2003 John Wiley &amp; Sons, Ltd.
Improved high-Tcsuperconducting quantum interference filters for sensitive magnetometry
2003-10-31

Superconducting quantum interference filters (SQIFs) are arrays of superconducting loops, with Josephson junctions, of diverse loop sizes. The dependence of the SQIF voltage on external magnetic fields is non-periodic and shows only one unique peak at zero field. We present several kinds of SQIFs—serial arrays, parallel arrays and various combinations of both—which are all realized with high-Tc superconductors. Compared to a single SQUID all SQIF types show improved magnetic field sensitivity and noise-limited field resolution. In order to realize really sensitive magnetometers the SQIFs were coupled to pickup coils. Consequently, the sensitivity and noise of the SQIF-based magnetometers are comparable with that of their SQUID-based counterparts. For a flip-chip configuration using a serial–parallel SQIF and a superconducting flux transformer, a noise-limited field resolution of 70 fT Hz−1/2 was achieved. This is only twice the value of that using a normal SQUID. Further reduction should be possible by a better adaptation of the complete design to the SQIF options.
Arginine physiology and its implication for wound healing
2003-11-01

Arginine is a basic amino acid that plays several pivotal roles in cellular physiology. Like any amino acid, it is involved with protein synthesis, but it is also intimately involved with cell signaling through the production of nitric oxide and cell proliferation through its metabolism to ornithine and the other polyamines. Because of these multiple functions, arginine is an essential substrate for wound healing processes. Numerous studies have shown that arginine supplementation can lead to normalization or improvement of healing. This article reviews the basic biochemistry and cell signaling within which arginine performs its functions. In particular, the requirement for this amino acid in tissue repair is highlighted. (WOUND REP REG 2003;11:419–423)
Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis.
2003-11-01

Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.
Urea Transport by Nitrogen-Regulated Tonoplast Intrinsic Proteins in Arabidopsis
2003-11-01

Abstract Urea is the major nitrogen (N) form supplied as fertilizer in agricultural plant production and also an important N metabolite in plants. Because urea transport in plants is not well understood, the aim of the present study was to isolate urea transporter genes from the model plant Arabidopsis. Using heterologous complementation of a urea uptake-defective yeast (Saccharomyces cerevisiae) mutant allowed to isolate AtTIP1;1, AtTIP1;2, AtTIP2;1, and AtTIP4;1 from a cDNA library of Arabidopsis. These cDNAs encode channel-like tonoplast intrinsic proteins (TIPs) that belong to the superfamily of major intrinsic proteins (or aquaporins). All four genes conferred growth of a urea uptake-defective yeast mutant on 2 mm urea in a phloretin-sensitive and pH-independent manner. Uptake studies using 14C-labeled urea into AtTIP2;1-expressing Xenopus laevis oocytes demonstrated that AtTIP2;1 facilitated urea transport also in a pH-independent manner and with linear concentration dependency. Expression studies showed that AtTIP1;2, AtTIP2;1, and AtTIP4;1 genes were up-regulated during early germination and under N deficiency in roots but constitutively expressed in shoots. Subcellular localization of green fluorescent protein-fused AtTIPs indicated that AtTIP1;2, AtTIP2;1, and AtTIP4;1 were targeted mainly to the tonoplast and other endomembranes. Thus, in addition to their role as water channels, TIP transporters may play a role in equilibrating urea concentrations between different cellular compartments.
Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing
2003-11-01

For many years, lactate has been known to accelerate collagen deposition in cultured fibroblasts and, without detailed explanation, has been presumed to stimulate angiogenesis. Similarly, hypoxia has been linked to angiogenic effects and collagen deposition from cultured cells. Paradoxically, however, wound angiogenesis and collagen deposition are increased by breathing oxygen and decreased by hypoxia. Lactate accumulates to 4–12 mM in wounds for several reasons, only one of which is the result of hypoxia. Oxygen in wounds is usually low but can be increased by breathing oxygen (without change in lactate). We have reported that lactate elicits vascular endothelial growth factor (VECF) from macrophages, as well as collagen, some heat shock proteins, and VECF from endothelial cells, and collagen from fibroblasts, even in the presence of normal amounts of oxygen. Hypoxia exerts many of these same effects in cultured cells. In this study, we elevated extracellular lactate in wounds by implanting purified solid‐state, hydrolysable polyglycolide. A steady‐state 2–3 mM additional elevation of lactate resulted. With it, there was a significant short‐term elevation of interleukin‐1β, a long‐term elevation of VECF (2×) and transforming growth factor‐β1 (2–3×), a 50% elevation in collagen deposition, and a large reduction of insulin‐like growth factor‐1 (− 90%). We propose that lactate induces a biochemical “perception” of hypoxia and instigates several signals that activate growth factor/cytokine signals while the continued presence of molecular oxygen allows endothelial cells and fibroblasts to reproduce and deposit collagen. The data are consistent with ADP‐ribosylation effects and oxidant signaling. (WOUND REP REG 2003;11:504–509)
Inhibition of Erythrocyte Cation Channels by Erythropoietin
2003-11-01

ABSTRACT. Recombinant human erythropoietin therapy is used to counteract anemia that is the result of renal insufficiency. It stimulates the formation of peripheral blood erythrocytes by inhibiting apoptosis of erythrocyte precursor cells. Mature erythrocytes have similarly been shown to undergo apoptosis. Hyperosmotic shock and Cl − removal activate a Ca 2+ -permeable, ethylisopropylamiloride-inhibitable cation channel. The subsequent increase of cytosolic Ca 2+ activates a scramblase that breaks down cell membrane phosphatidylserine asymmetry, leading to annexin binding. Studied was whether channel activity and erythrocyte cell death are regulated by erythropoietin. Scatchard plot analysis disclosed low-abundance, high-affinity binding of 125 I-erythropoietin to erythrocytes. Whole cell patch clamp experiments revealed significant inhibition of the ethylisopropylamiloride-sensitive current by 1 U/ml erythropoietin. Cl − removal triggered annexin binding, an effect abrogated by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). Osmotic shock (700 mOsm) stimulated annexin binding within 24 h in the majority of the erythrocytes, an effect blunted by erythropoietin (1 U/ml) but not by GM-CSF (10 ng/ml). In the nominal absence of Ca 2+ , the effect of osmotic shock was blunted and the effect of erythropoietin abolished. In hemodialysis patients, intravenous administration of erythropoietin (50 IU/kg) within 4 h decreased the number of annexin binding circulating erythrocytes. Erythropoietin binds to erythrocytes and inhibits volume-sensitive erythrocyte cation channels and thus the breakdown of phosphatidylserine asymmetry after activation of this channel. The effect could prolong the erythrocyte lifespan and may contribute to the enhancement of the erythrocyte number during erythropoietin therapy in dialysis patients. E-mail: florian.lang@uni-tuebingen.de
Water solubility in carbonatite melts
2003-11-01

Water solubility in Ca-Na-Mg carbonate melt was measured at 900 °C from 0.25 to 2.25 kbar using a modified double-capsule technique and rapid-quench cold-seal vessels. The data can be described by the empirical relationship W = 8.705 P0.635, where W is water solubility in weight percent and P is pressure in kbar. The relative error in water solubility calculated by this equation is estimated to be about 15%. Already at 1 kbar, water solubility reaches nearly 10 wt%, which is two to three times the value observed for most silicate melts under similar conditions. The exceptionally high water solubility in carbonatite magmas together with the preferential partitioning of alkalis into a coexisting fluid phase may explain the massive aqueous metasomatism (fenitisation) usually observed around intrusive carbonatite bodies.