A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System x\u3csub\u3ec\u3c/sub\u3e\u3csup\u3e−\u3c/sup\u3e Mediates Aglycemic Neuronal Cell Death

The astrocyte cystine/glutamate antiporter (system xc−) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc− expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc− mediates aglycemic neuronal cell death

Classification and analysis of emission-line galaxies using mean field independent component analysis

We present an analysis of the optical spectra of narrow emission-line galaxies, based on mean field independent component analysis (MFICA). Samples of galaxies were drawn from the Sloan Digital Sky Survey (SDSS) and used to generate compact sets of `continuum' and `emission-line' component spectra. These components can be linearly combined to reconstruct the observed spectra of a wider sample of galaxies. Only 10 components - five continuum and five emission line - are required to produce accurate reconstructions of essentially all narrow emission-line galaxies; the median absolute deviations of the reconstructed emission-line fluxes, given the signal-to-noise ratio (S/N) of the observed spectra, are 1.2-1.8 sigma for the strong lines. After applying the MFICA components to a large sample of SDSS galaxies we identify the regions of parameter space that correspond to pure star formation and pure active galactic nucleus (AGN) emission-line spectra, and produce high S/N reconstructions of these spectra. The physical properties of the pure star formation and pure AGN spectra are investigated by means of a series of photoionization models, exploiting the faint emission lines that can be measured in the reconstructions. We are able to recreate the emission line strengths of the most extreme AGN case by assuming the central engine illuminates a large number of individual clouds with radial distance and density distributions, f(r) ~ r^gamma and g(n) ~ n^beta, respectively. The best fit is obtained with gamma = -0.75 and beta = -1.4. From the reconstructed star formation spectra we are able to estimate the starburst ages. These preliminary investigations serve to demonstrate the success of the MFICA-based technique in identifying distinct emission sources, and its potential as a tool for the detailed analysis of the physical properties of galaxies in large-scale surveys.Comment: MNRAS accepted. 29 pages, 24 figures, 3 table

Interpreting the Ionization Sequence in AGN Emission-Line Spectra

We investigate the physical cause of the great range in the ionization level seen in the spectra of narrow lined active galactic nuclei (AGN). Mean field independent component analysis identifies examples of individual SDSS galaxies whose spectra are not dominated by emission due to star formation (SF), which we designate as AGN. We assembled high S/N ratio composite spectra of a sequence of these AGN defined by the ionization level of their narrow-line regions (NLR), extending down to very low-ionization cases. We used a local optimally emitting cloud (LOC) model to fit emission-line ratios in this AGN sequence. These included the weak lines that can be measured only in the co-added spectra, providing consistency checks on strong line diagnostics. After integrating over a wide range of radii and densities our models indicate that the radial extent of the NLR is the major parameter in determining the position of high to moderate ionization AGN along our sequence, providing a physical interpretation for their systematic variation. Higher ionization AGN contain optimally emitting clouds that are more concentrated towards the central continuum source than in lower ionization AGN. Our LOC models indicate that for the objects that lie on our AGN sequence, the ionizing luminosity is anticorrelated with the NLR ionization level, and hence anticorrelated with the radial concentration and physical extent of the NLR. A possible interpretation that deserves further exploration is that the ionization sequence might be an age sequence where low ionization objects are older and have systematically cleared out their central regions by radiation pressure. We consider that our AGN sequence instead represents a mixing curve of SF and AGN spectra, but argue that while many galaxies do have this type of composite spectra, our AGN sequence appears to be a special set of objects with negligible SF excitation.Comment: 57 pages; 18 figures, accepted by MNRA

Interpreting the Ionization Sequence in Star-Forming Galaxy Emission-Line Spectra

High ionization star forming (SF) galaxies are easily identified with strong emission line techniques such as the BPT diagram, and form an obvious ionization sequence on such diagrams. We use a locally optimally emitting cloud model to fit emission line ratios that constrain the excitation mechanism, spectral energy distribution, abundances and physical conditions along the star-formation ionization sequence. Our analysis takes advantage of the identification of a sample of pure star-forming galaxies, to define the ionization sequence, via mean field independent component analysis. Previous work has suggested that the major parameter controlling the ionization level in SF galaxies is the metallicity. Here we show that the observed SF- sequence could alternatively be interpreted primarily as a sequence in the distribution of the ionizing flux incident on gas spread throughout a galaxy. Metallicity variations remain necessary to model the SF-sequence, however, our best models indicate that galaxies with the highest and lowest observed ionization levels (outside the range -0.37 < log [O III]/H\b{eta} < -0.09) require the variation of an additional physical parameter other than metallicity, which we determine to be the distribution of ionizing flux in the galaxy.Comment: 41 pages, 17 figures, 9 tables, accepted to MNRA

Theology, News and Notes - Vol. 12, No. 01

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1189/thumbnail.jp

Supersymmetry Without Prejudice at the 7 TeV LHC

We investigate the model independent nature of the Supersymmetry search strategies at the 7 TeV LHC. To this end, we study the missing-transverse-energy-based searches developed by the ATLAS Collaboration that were essentially designed for mSUGRA. We simulate the signals for ~71k models in the 19-dimensional parameter space of the pMSSM. These models have been found to satisfy existing experimental and theoretical constraints and provide insight into general features of the MSSM without reference to a particular SUSY breaking scenario or any other assumptions at the GUT scale. Using backgrounds generated by ATLAS, we find that imprecise knowledge of these estimated backgrounds is a limiting factor in the potential discovery of these models and that some channels become systematics-limited at larger luminosities. As this systematic error is varied between 20-100%, roughly half to 90% of this model sample is observable with significance S>5 for 1 fb^{-1} of integrated luminosity. We then examine the model characteristics for the cases which cannot be discovered and find several contributing factors. We find that a blanket statement that squarks and gluinos are excluded with masses below a specific value cannot be made. We next explore possible modifications to the kinematic cuts in these analyses that may improve the pMSSM model coverage. Lastly, we examine the implications of a null search at the 7 TeV LHC in terms of the degree of fine-tuning that would be present in this model set and for sparticle production at the 500 GeV and 1 TeV Linear Collider.Comment: 51 pages, 26 figure

Theology, News and Notes - Vol. 04, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1181/thumbnail.jp

Türk-Ermeni ilişkileri

Taha Toros Arşivi, Dosya No: 77/A-Ermeniler. Not: Gazetenin"Düşünenlerin Düşüncesi" köşesinde yayımlanmıştır.İstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Non-cell autonomous influence of the astrocyte system xc− on hypoglycaemic neuronal cell death

Despite longstanding evidence that hypoglycaemic neuronal injury is mediated by glutamate excitotoxicity, the cellular and molecular mechanisms involved remain incompletely defined. Here, we demonstrate that the excitotoxic neuronal death that follows GD (glucose deprivation) is initiated by glutamate extruded from astrocytes via system xc− – an amino acid transporter that imports l-cystine and exports l-glutamate. Specifically, we find that depriving mixed cortical cell cultures of glucose for up to 8 h injures neurons, but not astrocytes. Neuronal death is prevented by ionotropic glutamate receptor antagonism and is partially sensitive to tetanus toxin. Removal of amino acids during the deprivation period prevents – whereas addition of l-cystine restores – GD-induced neuronal death, implicating the cystine/glutamate antiporter, system xc−. Indeed, drugs known to inhibit system xc− ameliorate GD-induced neuronal death. Further, a dramatic reduction in neuronal death is observed in chimaeric cultures consisting of neurons derived from WT (wild-type) mice plated on top of astrocytes derived from sut mice, which harbour a naturally occurring null mutation in the gene (Slc7a11) that encodes the substrate-specific light chain of system xc− (xCT). Finally, enhancement of astrocytic system xc− expression and function via IL-1β (interleukin-1β) exposure potentiates hypoglycaemic neuronal death, the process of which is prevented by removal of l-cystine and/or addition of system xc− inhibitors. Thus, under the conditions of GD, our studies demonstrate that astrocytes, via system xc−, have a direct, non-cell autonomous effect on cortical neuron survival