Characterization of [3H][^3H]Phenobarbital Binding to Rat Brain Membranes

The binding of $[^3H]$phenobarbital to rat brain membranes was studied in order to determine its characteristics and specificity. The binding reaction was rapid and occurred at sites of low affinity. $(K_d = 700 μM)$ and very high density $(B_{max} = 2.7 nmoll/mg protein)$. It was unaffected by temperature changes from O°C to 95°C and was maximal at pH 5. Detergents in low concentrations markedly decreased the binding, apparently without solubilizing the binding sites. It is concluded that the binding of $[^3H]$ phenobarbital is a rather non-specific interaction with the plasma membrane

Projecting Pharmaceutical Expenditure in EU5 to 2021: Adjusting for the Impact of Discounts and Rebates

Within (European) healthcare systems, the main goal for pharmaceutical expenditure is cost containment. This is due to a general belief among healthcare policy makers that pharmaceutical expenditure—driven by high prices—will be unsustainable unless further reforms are enacted.The aim of the research published in this paper is to provide more realistic expectations of pharmaceutical expenditure for all key stakeholder groups by estimating pharmaceutical expenditure at ‘net’ prices. We also aim to estimate any gaps developing between list and net pharmaceutical expenditure for the EU5 countries (i.e. France, Germany, Italy, Spain, and the UK). We adjusted an established forecast of pharmaceutical expenditure for the EU5 countries, from 2017 to 2021, by reflecting discounts and rebates not previously considered, i.e. we moved from ‘list’ to ‘net’ prices, as far as data were available.We found an increasing divergence between expenditure measured at list and net prices. When the forecasts for the five countries were aggregated, the EU5 (unweighted) average historical growth (2010–2016) rate fell from 3.4% compound annual growth rate at list to 2.5% at net. For the forecast, the net growth rate was estimated at 1.5 versus 2.9% at list.Our results suggest that future growth in pharmaceutical expenditure in Europe is likely to be (1) lower than previously understood from forecasts based on list prices and (2) below predicted healthcare expenditure growth in Europe and in line with long-term economic growth rates. For policy makers concerned about the sustainability of pharmaceutical expenditure, this study may provide some comfort, in that the perceived problem is not as large as expected

Width of Sunspot Generating Zone and Reconstruction of Butterfly Diagram

Based on the extended Greenwich-NOAA/USAF catalogue of sunspot groups it is demonstrated that the parameters describing the latitudinal width of the sunspot generating zone (SGZ) are closely related to the current level of solar activity, and the growth of the activity leads to the expansion of SGZ. The ratio of the sunspot number to the width of SGZ shows saturation at a certain level of the sunspot number, and above this level the increase of the activity takes place mostly due to the expansion of SGZ. It is shown that the mean latitudes of sunspots can be reconstructed from the amplitudes of solar activity. Using the obtained relations and the group sunspot numbers by Hoyt and Schatten (1998), the latitude distribution of sunspot groups ("the Maunder butterfly diagram") for the 18th and the first half of the 19th centuries is reconstructed and compared with historical sunspot observations.Comment: 16 pages, 11 figures; accepted by Solar Physics; the final publication will be available at www.springerlink.co

Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement

G protein-coupled receptors (GPCRs) are key biological switches that transmit both internal and external stimuli into the cell interior. Among the GPCRs, the "light receptor" rhodopsin has been shown to activate with a rearrangement of the transmembrane (TM) helix bundle within ~1 ms, while all other receptors are thought to become activated within ~50 ms to seconds at saturating concentrations. Here, we investigate synchronous stimulation of a dimeric GPCR, the metabotropic glutamate receptor type 1 (mGluR1), by two entirely different methods: (i) UV light-triggered uncaging of glutamate in intact cells or (ii) piezo-driven solution exchange in outside-out patches. Submillisecond FRET recordings between labels at intracellular receptor sites were used to record conformational changes in the mGluR1. At millimolar ligand concentrations, the initial rearrangement between the mGluR1 subunits occurs at a speed of τ(1) ~ 1-2 ms and requires the occupancy of both binding sites in the mGluR1 dimer. These rapid changes were followed by significantly slower conformational changes in the TM domain (τ(2) ~ 20 ms). Receptor deactivation occurred with time constants of ~40 and ~900 ms for the inter- and intrasubunit conformational changes, respectively. Together, these data show that, at high glutamate concentrations, the initial intersubunit activation of mGluR1 proceeds with millisecond speed, that there is loose coupling between this initial step and activation of the TM domain, and that activation and deactivation follow a cyclic pathway, including-in addition to the inactive and active states-at least two metastable intermediate states

Entwicklung eines zeitlichen und räumlichen Entscheidungshilfesystems gegen den Erbsenwickler (Cydia nigricana, Fabricius)

Pea moths (Cydia nigricana) can cause severe damages in pea crops (Pisum sativum). Larvae feed on the seeds in the pods and contaminate them with feces. In the cultivation of organic green peas 0.5 % damaged seeds lead to the denial of whole pea fields (Schulz & Saucke 2005). There can be a yield loss in forage peas and a loss of quality of seeds for propagation. Within the framework of the project to improve the spatial and temporal cultivation strategy of peas to get less damage due to pea moths, is the intention. For a better spatial and temporal cultivation strategy, the DSS creates a map with areas with an infestation risk factor. The higher the risk factor, the earlier the new fields should be cultivated. Therefore, the first part of the DSS works with georeferenced data, like distances between fields of the previous year and the currently planned fields and their infestation risk. The coincidence of the flowering of peas and the flight of pea moths is very important for the infestation. Hence, the second part of the DSS predicts the phenology of the pea and the development of the pea moth for a better precision of the pest control

Erbsenwickler (Cydia nigricana) in Gemüse- und Körnererbsen: Grundlagen zur Befallsprognose und Schadensprävention

Spatio-temporal distribution, combined with aspects of insect biology and ecology can influence the infestation risk of the key pea pest Cydia nigricana in vegetable- and field peas. The proximity of pea fields of the previous cultivation period highly affects the infestation potential of the moth. The presented study aims to monitor the infestation development in three different regions in Germany (North Hesse, Saxony, Saxony-Anhalt) in four consecutive years and to relate empirical pest incidences to key factors as crop abundance, the distance to previous pea fields, the pea plant phenology and climatic conditions. In a next step, these data will form the basis for the elaboration of a computer-aided decision support system, which assists farmers in implementing preventive strategies based on risk avoidance

The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction across a tunneling junction out of equilibrium

The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction between two magnetic $s$-$d$ spin impurities across a tunneling junction is studied when the system is driven out of equilibrium through biasing the junction. The nonequilibrium situation is handled with the Keldysh time-loop perturbation formalism in conjunction with appropriate coupling methods for tunneling systems due to Caroli and Feuchtwang. We find that the presence of a nonequilibrium bias across the junction leads to an interference of several fundamental oscillations, such that in this tunneling geometry, it is possible to tune the interaction between ferromagnetic and antiferromagnetic coupling at a fixed impurity configuration, simply by changing the bias across the junction. Furthermore, it is shown that the range of the RKKY interaction is altered out of equilibrium, such that in particular the interaction energy between two slabs of spins scales extensively with the thickness of the slabs in the presence of an applied bias.Comment: 38 pages revtex preprint; 5 postscript figures; submitted to Phys. Rev.

The phase relation between sunspot numbers and soft X-ray flares

To better understand long-term flare activity, we present a statistical study on soft X-ray flares from May 1976 to May 2008. It is found that the smoothed monthly peak fluxes of C-class, M-class, and X-class flares have a very noticeable time lag of 13, 8, and 8 months in cycle 21 respectively with respect to the smoothed monthly sunspot numbers. There is no time lag between the sunspot numbers and M-class flares in cycle 22. However, there is a one-month time lag for C-class flares and a one-month time lead for X-class flares with regard to sunspot numbers in cycle 22. For cycle 23, the smoothed monthly peak fluxes of C-class, M-class, and X-class flares have a very noticeable time lag of one month, 5 months, and 21 months respectively with respect to sunspot numbers. If we take the three types of flares together, the smoothed monthly peak fluxes of soft X-ray flares have a time lag of 9 months in cycle 21, no time lag in cycle 22 and a characteristic time lag of 5 months in cycle 23 with respect to the smoothed monthly sunspot numbers. Furthermore, the correlation coefficients of the smoothed monthly peak fluxes of M-class and X-class flares and the smoothed monthly sunspot numbers are higher in cycle 22 than those in cycles 21 and 23. The correlation coefficients between the three kinds of soft X-ray flares in cycle 22 are higher than those in cycles 21 and 23. These findings may be instructive in predicting C-class, M-class, and X-class flares regarding sunspot numbers in the next cycle and the physical processes of energy storage and dissipation in the corona.Comment: 8 pages, 3 figures, Accepted for publication in Astrophysics & Space Scienc

Aharonov-Bohm cages in two-dimensional structures

We present an extreme localization mechanism induced by a magnetic field for tight-binding electrons in two-dimensional structures. This spectacular phenomenon is investigated for a large class of tilings (periodic, quasiperiodic, or random). We are led to introduce the Aharonov-Bohm cages defined as the set of sites eventually visited by a wavepacket that can, for particular values of the magnetic flux, be bounded. We finally discuss the quantum dynamics which exhibits an original pulsating behaviour.Comment: 4 pages Latex, 3 eps figures, 1 ps figur