Modulation of calcium and potassium currents by lamotrigine

Actions of the new antiepileptic drug lamotrigine (LTG) were characterized using extracellular and whole cell patch clamp recordings from rat CAI and CA3 pyramidal cells in vitro. The results suggest that LTG, beside its previously described effect on the fast sodium inward current, also modulates - presumably voltage-gated - calcium currents and the transient potassium outward current ID. These may be effective mechanisms to inhibit pathological excitation in epilepsy and may be of potential benefit in treating: underlying cellular disturbances in bipolar disorder

Laser-induced fluorescence studies of HfF+ produced by autoionization

Autoionization of Rydberg states of HfF, prepared using the optical-optical double resonance (OODR) technique, holds promise to create HfF+ in a particular Zeeman level of a rovibronic state for an electron electric dipole moment (eEDM) search. We characterize a vibronic band of Rydberg HfF at 54 cm-1 above the lowest ionization threshold and directly probe the state of the ions formed from this vibronic band by performing laser-induced fluorescence (LIF) on the ions. The Rydberg HfF molecules show a propensity to decay into only a few ion rotational states of a given parity and are found to preserve their orientation qualitatively upon autoionization. We show empirically that we can create 30% of the total ion yield in a particular |J+,M+> state and present a simplified model describing autoionization from a given Rydberg state that assumes no angular dynamics.Comment: 8 pages, 5 figure

Fundamental Neutron Physics at Spallation Sources

Low-energy neutrons have been a useful probe in fundamental physics studies for more than 70 years. With advances in accelerator technology, many new sources are spallation based. These new, high-flux facilities are becoming the sites for many next-generation fundamental neutron physics experiments. In this review, we present an overview of the sources and the current and upcoming fundamental neutron physics programs

Safety of Log Transportation After Regulation and Training in the State of Georgia, USA

Mechanical failure rates observed in highway accidents involving logging tractor-trailers have fallen significantly since Georgia subjected these vehicles to random roadside inspections. This improvement is attributed to both the regulation and the training efforts aimed at the log trucking community immediately before and after the implementation of the rules

Identification of the heart as the critical site of adenosine mediated embryo protection

<p>Abstract</p> <p>Background</p> <p>Our understanding of the mechanisms that protect the developing embryo from intrauterine stress is limited. Recently, adenosine has been demonstrated to play a critical role in protecting the embryo against hypoxia via adenosine A1 receptors (A1ARs), which are expressed in the heart, nervous system, and other sites during development. However, the sites of A1AR action that mediate embryo protection are not known. To determine if the heart is a key site of adenosine-mediated embryo protection, A1ARs were selectively deleted in the embryonic heart using a Cre-LoxP system in which the alpha-myosin heavy chain promoter drives Cre-recombinase expression and excision of the A1AR gene from cardiomyocytes.</p> <p>Results</p> <p>With increasing exposure of maternal hypoxia (10% O₂) from 48-96 hours beginning at embryonic day (E) 8.5, embryo viability decreased in the cardiac-A1AR deleted embryos. 48 hours of hypoxia reduced embryonic viability by 49% in embryos exposed from E10.5-12.5 but no effect on viability was observed in younger embryos exposed to hypoxia from E8.5-10.5. After 72 hours of hypoxia, 57.8% of the cardiac-A1AR deleted embryos were either dead or re-absorbed compared to 13.7% of control littermates and after 96 hours 81.6% of cardiac-A1AR deleted embryos were dead or re-absorbed. After 72 hours of hypoxia, cardiac size was reduced significantly more in the cardiac-A1AR deleted hearts compared to controls. Gene expression analysis revealed clusters of genes that are regulated by both hypoxia and A1AR expression.</p> <p>Conclusions</p> <p>These data identify the embryonic heart as the critical site where adenosine acts to protect the embryo against hypoxia. As such these studies identify a previously unrecognized mechanism of embryo protection.</p

The Host Galaxy and Central Engine of the Dwarf AGN POX 52

We present new multi-wavelength observations of the dwarf Seyfert 1 galaxy POX 52 in order to investigate the properties of the host galaxy and the active nucleus, and to examine the mass of its black hole, previously estimated to be ~ 10^5 M_sun. Hubble Space Telescope ACS/HRC images show that the host galaxy has a dwarf elliptical morphology (M_I = -18.4 mag, Sersic index n = 4.3) with no detected disk component or spiral structure, confirming previous results from ground-based imaging. X-ray observations from both Chandra and XMM show strong (factor of 2) variability over timescales as short as 500 s, as well as a dramatic decrease in the absorbing column density over a 9 month period. We attribute this change to a partial covering absorber, with a 94% covering fraction and N_H = 58^{+8.4}_{-9.2} * 10^21 cm^-2, that moved out of the line of sight in between the XMM and Chandra observations. Combining these data with observations from the VLA, Spitzer, and archival data from 2MASS and GALEX, we examine the spectral energy distribution (SED) of the active nucleus. Its shape is broadly similar to typical radio-quiet quasar SEDs, despite the very low bolometric luminosity of L_bol = 1.3 * 10^43 ergs/s. Finally, we compare black hole mass estimators including methods based on X-ray variability, and optical scaling relations using the broad H-beta line width and AGN continuum luminosity, finding a range of black hole mass from all methods to be M_bh = (2.2-4.2) * 10^5 M_sun, with an Eddington ratio of L_bol/L_edd = 0.2-0.5.Comment: 19 pages, 16 figures, accepted for publication in Ap

The statistical mechanics of complex signaling networks : nerve growth factor signaling

It is becoming increasingly appreciated that the signal transduction systems used by eukaryotic cells to achieve a variety of essential responses represent highly complex networks rather than simple linear pathways. While significant effort is being made to experimentally measure the rate constants for individual steps in these signaling networks, many of the parameters required to describe the behavior of these systems remain unknown, or at best, estimates. With these goals and caveats in mind, we use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. To establish the usefulness of our approach, we have applied our methods towards modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. Using our approach, we are able to extract predictions that are highly specific and accurate, thereby enabling us to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. We show that extracting biologically relevant predictions from complex signaling models appears to be possible even in the absence of measurements of all the individual rate constants. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems wherein particular ''soft'' combinations of parameters can be varied over wide ranges without impacting the final output and demonstrating that a few ''stiff'' parameter combinations center around the paramount regulatory steps of the network. We refer to this property -- which is distinct from robustness -- as ''sloppiness.''Comment: 24 pages, 10 EPS figures, 1 GIF (makes 5 multi-panel figs + caption for GIF), IOP style; supp. info/figs. included as brown_supp.pd