Postsynaptic protein kinase a reduces neuronal excitability in response to increased synaptic excitation in the Drosophila CNS

Previous work has identified a role for synaptic activity in the development of excitable properties of motoneurons in the Drosophila embryo. In this study the underlying mechanism that enables two such neurons, termed aCC and RP2, to respond to increased exposure to synaptic excitation is characterized. Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase (EC:3.1.4, dunce) or acetylcholinesterase (EC:3.1.1.7, ace), the enzyme that terminates the endogenous cholinergic excitation of these motoneurons. Analysis of membrane excitability in aCC/RP2, in either background, shows that these neurons have a significantly reduced capability to fire action potentials (APs) in response to injection of depolarizing current. Analysis of underlying voltage-gated currents show that this effect is associated with a marked reduction in magnitude of the voltage-dependent inward Na+ current (INa). Partially blocking INa in these motoneurons, using low concentrations of TTX, demonstrates that a reduction of INa is, by itself, sufficient to reduce membrane excitability. An analysis of firing implicates an increased AP threshold to underlie the reduction in membrane excitability observed because of heightened exposure to synaptic excitation. Genetic or pharmacological manipulations that either elevate cAMP or increase protein kinase A (PKA) activity in wild-type aCC/RP2 mimic both the reductions in membrane excitability and INa. In comparison, increasing cAMP catabolism or inhibition of PKA activity is sufficient to block the induction of these activity-dependent changes. The induced changes in excitability can be rapid, occurring within 5 min of exposure to a membrane-permeable cAMP analog, indicative that threshold can be regulated in these neurons by a post-translational mechanism that is dependent on phosphorylation

On the Coexistence Magnetism/Superconductivity in the Heavy-Fermion Superconductor CePt3_3Si

The interplay between magnetism and superconductivity in the newly discovered heavy-fermion superconductor CePt$_3$Si has been investigated using the zero-field $\mu$SR technique. The $\mu$SR data indicate that the whole muon ensemble senses spontaneous internal fields in the magnetic phase, demonstrating that magnetism occurs in the whole sample volume. This points to a microscopic coexistence between magnetism and heavy-fermion superconductivity.Comment: Final version, new figure structure, references correcte

Hydraulic flow through a channel contraction: multiple steady states

We have investigated shallow water flows through a channel with a contraction by experimental and theoretical means. The horizontal channel consists of a sluice gate and an upstream channel of constant width $b_0$ ending in a linear contraction of minimum width $b_c$. Experimentally, we observe upstream steady and moving bores/shocks, and oblique waves in the contraction, as single and multiple steady states, as well as a steady reservoir with a complex hydraulic jump in the contraction occurring in a small section of the $b_c/b_0$ and Froude number parameter plane. One-dimensional hydraulic theory provides a comprehensive leading-order approximation, in which a turbulent frictional parametrization is used to achieve quantitative agreement. An analytical and numerical analysis is given for two-dimensional supercritical shallow water flows. It shows that the one-dimensional hydraulic analysis for inviscid flows away from hydraulic jumps holds surprisingly well, even though the two-dimensional oblique hydraulic jump patterns can show large variations across the contraction channel

'White knuckle care work' : violence, gender and new public management in the voluntary sector

Drawing on comparative data from Canada and Scotland, this article explores reasons why violence is tolerated in non-profit care settings. This article will provide insights into how workers' orientations to work, the desire to care and the intrinsic rewards from working in a non-profit context interact with the organization of work and managerially constructed workplace norms and cultures (Burawoy, 1979) to offset the tensions in an environment characterized by scarce resources and poor working conditions. This article will also outline how the same environment of scarce resources causes strains in management's efforts to establish such cultures. Working with highly excluded service users with problems that do not respond to easy interventions, workers find themselves working at the edge of their endurance, hanging on by their fingernails, and beginning to participate in various forms of resistance; suggesting that even among the most highly committed, 'white knuckle care' may be unsustainable

Problems Facing the Pharmaceutical Industry and Approaches to Ensure Long Term Viability

This paper examines the Pharmaceutical (Pharma) industry and the changes that have occurred particularly over the last 10 years as a result of the overall economic downturn, the rising cost of healthcare and the costs associated with the development and sales of pharmaceuticals. One response of big Pharma to this has been the recent spate of partnerships, mergers and acquisitions, consolidation, diversification, licensing agreements and downsizing in both human and capital resources. Four major challenges facing the complex Pharma industry are highlighted and discussed. These include the decline in the discovery, approval and marketing of new chemical entities (NCE) with fewer and fewer blockbuster drugs making it to the market, competition from generics drugs, regulatory pressures and the weak growth in the US market (the largest market) and therefore the need to explore other markets to name a few. In addition to the research driven aspect of the paper, a summary of the interviews conducted with executives and other industry practitioners (to get their personal views) is presented. Finally referencing some of the strategies adapted by some companies, this thesis identifies Organizational Dynamics areas of concentration and the role they can play within companies in their plans to ensure long term viability. The analysis focuses on the commercial aspects of the industry and offers some steps that will be useful in changing the current business model and setting the stage for future success

Magnetic order, spin waves and fluctuations in the triangular antiferromagnet La2Ca2MnO7

We report magnetic susceptibility, specific heat and muon spin relaxation (muSR) experiments on the triangular antiferromagnet La2Ca2MnO7 which develops a genuine two-dimensional, three-sublattice \sqrt{3} \times \sqrt{3} magnetic order below T_N = 2.8 K. From the susceptibility and specific heat data an estimate of the exchange interaction is derived. A value for the spin-wave gap is obtained from the latter data. The analysis of a previously reported inelastic neutron scattering study yields values for the exchange and spin-wave gap compatible with the results obtained from macroscopic measurements. An appreciable entropy is still missing at 10 K that may be ascribed to intense short-range correlations. The critical paramagnetic fluctuations extend far above T_N, and can be partly understood in terms of two-dimensional spin-wave excitations. While no spontaneous muSR field is observed below T_N, persistent spin dynamics is found. Short-range correlations are detected in this temperature range. Their relation to a possible molecular spin substructure and the observed exotic spin fluctuations is discussed.Comment: 9 pages, 6 figure

Evidence for unidimensional low-energy excitations as the origin of persistent spin dynamics in geometrically frustrated magnets

We report specific heat, magnetic, and muon spin relaxation measurements performed on a polycrystalline sample of the normal spinel CdHo2S4. The rare-earth ions sit on a lattice of corner-sharing regular tetrahedra as in pyrochlore compounds. Magnetic ordering is detected at Tc ~ 0.87 K. From spin-lattice relaxation rate measurements on both sides of Tc we uncover similar magnetic excitation modes driving the so-called persistent spin dynamics at T < Tc. Unidimensional excitations are argued to be at its origin. Often observed spin loop structures are suggested to support these excitations. The possibility of a generic mechanism for their existence is discussed.Comment: 7 pages, 8 figure

Anomalously slow spin dynamics and short-range correlations in the quantum spin ice systems Yb2Ti2O7 and Yb2Sn2O7

We report a positive muon spin relaxation and rotation (\muSR) study of the quantum spin ice materials Yb2Ti2O7 and Yb2Sn2O7 focusing on the low field response. In agreement with earlier reports, data recorded in small longitudinal fields evidence anomalously slow spin dynamics in the microsecond range below the temperature T_c at which the specific heat displays an intense peak, namely T_c = 0.24 K and 0.15 K, respectively, for the two systems. We found that slow dynamics extends above T_c up to at least 0.7 K for both compounds. The conventional dynamical Gaussian Kubo-Toyabe model describes the \muSR spectra recorded above T_c. At lower temperatures a published analytical extension of the Gaussian Kubo-Toyabe model provides a good description, consistent with the existence of short-range magnetic correlations. While the physical response of the two systems is qualitatively the same, Yb2Ti2O7 exhibits a much larger local magnetic susceptibility than Yb2Sn2O7 below T_c. Considering previously reported ac susceptibility, neutron scattering and \muSR results, we suggest the existence of anomalously slow spin dynamics to be a common physical property of pyrochlore magnetic materials. The possibility of molecular spin substructures to be associated to the slow dynamics and therefore the short-range correlations is mentioned. The slow spin dynamics observed under field does not exclude the presence of much faster dynamics detected in extremely low or zero field.Comment: 11 pages, 10 figure