Calcium-Permeable AMPA Receptors in the Retina

The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear. In this brief review, I will discuss recent progress toward understanding how Ca2+-permeable AMPA receptors (CP-GluARs) contribute to synaptic transmission and newly discovered forms of synaptic plasticity in the retina

Imperfect Space Clamp Permits Electrotonic Interactions between Inhibitory and Excitatory Synaptic Conductances, Distorting Voltage Clamp Recordings

The voltage clamp technique is frequently used to examine the strength and composition of synaptic input to neurons. Even accounting for imperfect voltage control of the entire cell membrane (“space clamp”), it is often assumed that currents measured at the soma are a proportional indicator of the postsynaptic conductance. Here, using NEURON simulation software to model somatic recordings from morphologically realistic neurons, we show that excitatory conductances recorded in voltage clamp mode are distorted significantly by neighboring inhibitory conductances, even when the postsynaptic membrane potential starts at the reversal potential of the inhibitory conductance. Analogous effects are observed when inhibitory postsynaptic currents are recorded at the reversal potential of the excitatory conductance. Escape potentials in poorly clamped dendrites reduce the amplitude of excitatory or inhibitory postsynaptic currents recorded at the reversal potential of the other conductance. In addition, unclamped postsynaptic inhibitory conductances linearize the recorded current-voltage relationship of excitatory inputs comprising AMPAR and NMDAR-mediated components, leading to significant underestimation of the relative contribution by NMDARs, which are particularly sensitive to small perturbations in membrane potential. Voltage clamp accuracy varies substantially between neurons and dendritic arbors of different morphology; as expected, more reliable recordings are obtained from dendrites near the soma, but up to 80% of the synaptic signal on thin, distant dendrites may be lost when postsynaptic interactions are present. These limitations of the voltage clamp technique may explain how postsynaptic effects on synaptic transmission could, in some cases, be attributed incorrectly to presynaptic mechanisms

Migraine Frequency and Health Utilities: Findings from a Multisite Survey

AbstractObjectivesAssess the relationship between migraine frequency and health utility.MethodsPatients aged ≥18 years diagnosed with episodic migraine were enrolled at three US sites representing varied models of health-care delivery. All subjects completed a questionnaire that included demographic and clinical information, a migraine-specific disability questionnaire, and the Health Utilities Index Mark 3 (HUI3). The HUI3 is a generic health status and health-related quality-of-life measure. HUI3 health status data are translated into utility scores anchored by 0 (dead) and 1 (perfect health).ResultsThe study enrolled 150 patients. The mean age was 44 years and 87% were female. Mean (±SD) monthly migraine frequency was 4.4 ± 3.6, with 34% reporting ≤2 migraines per month and 20% reporting >6 migraines per month. The mean (±SD) HUI3 score was 0.62 ± 0.26. After controlling for study center, demographics, comorbidities, migraine characteristics, and level of migraine disruptiveness, migraine frequency was found to be significantly (P < 0.05) and negatively associated with HUI3 scores. Subjects with >6 migraines per month had an adjusted mean HUI3 score of 0.41; the corresponding mean for those reporting ≤2 migraines per month was 0.67. Migraine frequency was positively associated with higher levels of disability for the emotion, cognition, and pain components of the HUI3.ConclusionsAmong this group of care-seeking patients, migraineurs' health utilities were inversely related to headache frequency. Although these data may not be generalizable to the entire migraine population, they may be useful in assessing the comparative cost-effectiveness of preventive migraine therapies

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

AEGIS: Demographics of X-ray and Optically Selected AGNs

We develop a new diagnostic method to classify galaxies into AGN hosts, star-forming galaxies, and absorption-dominated galaxies by combining the [O III]/Hbeta ratio with rest-frame U-B color. This can be used to robustly select AGNs in galaxy samples at intermediate redshifts (z<1). We compare the result of this optical AGN selection with X-ray selection using a sample of 3150 galaxies with 0.3<z<0.8 and I_AB<22, selected from the DEEP2 Galaxy Redshift Survey and the All-wavelength Extended Groth Strip International Survey (AEGIS). Among the 146 X-ray sources in this sample, 58% are classified optically as emission-line AGNs, the rest as star-forming galaxies or absorption-dominated galaxies. The latter are also known as "X-ray bright, optically normal galaxies" (XBONGs). Analysis of the relationship between optical emission lines and X-ray properties shows that the completeness of optical AGN selection suffers from dependence on the star formation rate and the quality of observed spectra. It also shows that XBONGs do not appear to be a physically distinct population from other X-ray detected, emission-line AGNs. On the other hand, X-ray AGN selection also has strong bias. About 2/3 of all emission-line AGNs at L_bol>10^44 erg/s in our sample are not detected in our 200 ks Chandra images, most likely due to moderate or heavy absorption by gas near the AGN. The 2--7 keV detection rate of Seyfert 2s at z~0.6 suggests that their column density distribution and Compton-thick fraction are similar to that of local Seyferts. Multiple sample selection techniques are needed to obtain as complete a sample as possible.Comment: 24 pages, 14 figures, submitted to ApJ. Version 2 matches the ApJ accepted version. Sec 3 was reorganized and partly rewritten with one additional figure (Fig.3

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50

We present dynamical modeling of the broad line region (BLR) in the Seyfert 1 galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN Monitoring Project (LAMP) 2011. We model the reverberation mapping data directly, constraining the geometry and kinematics of the BLR, as well as deriving a black hole mass estimate that does not depend on a normalizing factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of 25\pm10 degrees above the plane. We also constrain the inclination angle to be 9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the virial black hole mass estimate from traditional reverberation mapping analysis, we find the normalizing constant (virial coefficient) to be log10(f) = 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74 based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies. While our dynamical model includes the possibility of a net inflow or outflow in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure

Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection

Realistic astrophysical environments are turbulent due to the extremely high Reynolds numbers. Therefore, the theories of reconnection intended for describing astrophysical reconnection should not ignore the effects of turbulence on magnetic reconnection. Turbulence is known to change the nature of many physical processes dramatically and in this review we claim that magnetic reconnection is not an exception. We stress that not only astrophysical turbulence is ubiquitous, but also magnetic reconnection itself induces turbulence. Thus turbulence must be accounted for in any realistic astrophysical reconnection setup. We argue that due to the similarities of MHD turbulence in relativistic and non-relativistic cases the theory of magnetic reconnection developed for the non-relativistic case can be extended to the relativistic case and we provide numerical simulations that support this conjecture. We also provide quantitative comparisons of the theoretical predictions and results of numerical experiments, including the situations when turbulent reconnection is self-driven, i.e. the turbulence in the system is generated by the reconnection process itself. We show how turbulent reconnection entails the violation of magnetic flux freezing, the conclusion that has really far reaching consequences for many realistically turbulent astrophysical environments. In addition, we consider observational testing of turbulent reconnection as well as numerous implications of the theory. The former includes the Sun and solar wind reconnection, while the latter include the process of reconnection diffusion induced by turbulent reconnection, the acceleration of energetic particles, bursts of turbulent reconnection related to black hole sources as well as gamma ray bursts. Finally, we explain why turbulent reconnection cannot be explained by turbulent resistivity or derived through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection - Concepts and Applications", editors W. Gonzalez, E. N. Parke

Investor Competition Over Information and the Pricing of Information Asymmetry

Whether the information environment affects the cost of capital is a fundamental question in accounting and finance research. Relying on theories about competition between informed investors as well as the pricing of information asymmetry, we hypothesize a cross-sectional variation in the pricing of information asymmetry that is conditional on competition. We develop and validate empirical proxies for competition using the number and concentration of institutional investor ownership. Using these proxies, we find a lower pricing of information asymmetry when there is more competition. Overall, our results suggest that competition between informed investors has an important effect on how the information environment affects the cost of capital.Deloitte Foundatio