Analog modulation of mossy fiber transmission is uncoupled from changes in presynaptic Ca2+

Subthreshold somatic depolarization has been shown recently to modulate presynaptic neurotransmitter release in cortical neurons. To understand the mechanisms underlying this mode of signaling in the axons of dentate granule cells (hippocampal mossy fibers), we have combined two- photon Ca2+ imaging with dual-patch recordings from somata and giant boutons forming synapses on CA3 pyramidal cells. In intact axons, subthreshold depolarization propagates both orthodromically and antidromically, with an estimated length constant of 200-600 mu m depending on the signal waveform. Surprisingly, presynaptic depolarization sufficient to enhance glutamate release at mossy fiber-CA3 pyramidal cell synapses has no detectable effect on either basal Ca2+-dependent fluorescence or action-potential-evoked fluorescence transients in giant boutons. We further estimate that neurotransmitter release varies with presynaptic Ca2+ entry with a 2.5-power relationship and that depolarization-induced synaptic facilitation remains intact in the presence of high-affinity presynaptic Ca2+ buffers or after blockade of local Ca2+ stores. We conclude that depolarization-dependent modulation of transmission at these boutons does not rely on changes in presynaptic Ca2+

A study of the selective hydroconversion of biocarboxylic acids to bioalcohols over novel indium-nickel/zeolite catalysts using octanoic acid as model reactant

Octanoic acid (OA) was hydrotreated in a flow-through reactor at 21 bar total pressure and 240-340 °C over supported metal catalysts prepared from Ni-zeolites (A, X, P) by indium modification. The Ni-zeolites were activated first in H2 flow at 21 bar and 450 °C. While a fraction of the nickel got fully reduced, the zeolite structure became partially destructed. However, some nickel cations remained unreduced, therefore a large fraction of the crystalline zeolite structure was retained. The indium modification of the reduced Ni-zeolites generated bimetallic NiIn/Ni,H-zeolite catalysts having higher stability, hydroconversion activity, octanol selectivity, and lower hydrodecarbonylation activity than the parent partially destructed Ni-zeolite and the Adkins-type catalysts, commercially applied for the conversion of fatty acids to alcohols. © 2013 Akadémiai Kiadó, Budapest, Hungary

Enhancement of Electrical Conduction and Phonon Scattering in Ga2O3(ZnO)9-In2O3(ZnO)9 Compounds by Modification of Interfaces at the Nanoscale

The Ga2O3(ZnO)9 and In2O3(ZnO)9 homologous phases have attracted attention as thermoelectric (TE) oxides due to their layered structures. Ga2O3(ZnO)9 exhibits low thermal conductivity, while In2O3(ZnO)9 possesses higher electrical conductivity. The TE properties of the solid solution of Ga2O3(ZnO)9-In2O3(ZnO)9 were explored and correlated with changes in the crystal structure. High-quality (1−x)Ga2O3(ZnO)9-(ZnO)9 (x = 0.0 to 1.0) ceramics were prepared by the solid-state route using B2O3 and Nd2O3 as additives. The crystal structures were analysed by x-ray diffraction, high-resolution transmission electron microscopy and atomic resolution scanning transmission electron microscopy–high-angle annular dark field imaging–energy dispersive x-ray spectroscopy (STEM–HAADF–EDS) techniques. A layered superstructure with compositional modulations was observed in all samples in the (1−x)Ga2O3(ZnO)9-xIn2O3(ZnO)9 system. All the ceramics exhibited nanoscale structural features identified as Ga- and In-rich inversion boundaries (IBs). Substitution of 20 mol.% In (x = 0.2) in the Ga2O3(ZnO)9 compounds generated basal and pyramidal indium IBs typically found in the In2O3(ZnO)m system. The (Ga0.8In0.2)2O3(ZnO)9 compound does not exhibit the structural features of the Cmcm Ga2O3(ZnO)9 compound, which is formed by a stacking of Ga-rich IBs along the pyramidal plane of the wurtzite ZnO, but features that resemble the crystal structure exhibited by the R3¯¯¯m In2O3(ZnO)m with basal and pyramidal indium IBs. The structural changes led to improved TE performance. For example, (Ga0.8In0.2)2O3(ZnO)9 showed a low thermal conductivity of 2 W/m K and a high power factor of 150 μW/m K2 giving a figure of merit (ZT) of 0.07 at 900 K. This is the highest ZT for Ga2O3(ZnO)9-based homologous compounds and is comparable with the highest ZT reported for In2O3(ZnO)9 homologous compounds

Numerical characterisation of the rotational behaviour of grey cast iron tunnel joints

The structural assessment of segmental grey cast iron (GCI) tunnel linings to nearby construction is challenging due to the presence of the joints affecting the stiffness of the tunnel lining. This paper presents an extensive investigation, using 3D finite element (FE) analyses, into the bending moment-rotation (M-θ) behaviour of two GCI tunnel joint geometries. These two geometries correspond to standard running and station tunnels of the London Underground network. The contribution of this study is two-fold. i) The novel characterisation of the M-θ response enables the development of new models for simulating the mechanical response of GCI tunnel joints with structural elements which can be used in simplified, 2D geotechnical analysis for tunnel safety assessments. ii) The analyses provide insight into the behaviour of GCI tunnel linings that would be difficult to achieve through experimental and field observations alone. More specifically, the analyses show that when the bolts are removed from the joints the possibility of tensile failure can be disregarded; that the initial bolt preload influences the rotational stiffness only after some rotation has taken place and does not alter the bending moment of opening; and that the out-of-plane displacement restraint has little influence on the joint response

Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10–14 year old schoolchildren: the HAPPY study

Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness

Does timing of decisions in a mixed duopoly matter?

We determine the endogenous order of moves in a mixed pricesetting duopoly. In contrast to the existing literature on mixed oligopolies we establish the payo equivalence of the games with an exogenously given order of moves if the most plausible equilibrium is realized in the market. Hence, in this case it does not matter whether one becomes a leader or a follower. We also establish that replacing a private firm by a public firm in the standard Bertrand-Edgeworth game with capacity constraints increases social welfare and that a pure-strategy equilibrium always exists

Fair scans of the seesaw. Consequences for predictions on LFV processes

Usual analyses based on scans of the seesaw parameter-space can be biassed since they do not cover in a fair way the complete parameter-space. More precisely, we show that in the common "R-parametrization", many acceptable R-matrices, compatible with the perturbativity of Yukawa couplings, are normally disregarded from the beginning, which produces biasses in the results. We give a straightforward procedure to scan the space of complex R-matrices in a complete way, giving a very simple rule to incorporate the perturbativity requirement as a condition for the entries of the R-matrix, something not considered before. As a relevant application of this, we show that the extended believe that BR(mu --> e, gamma) in supersymmetric seesaw models depends strongly on the value of theta_13 is an "optical effect" produced by such biassed scans, and does not hold after a careful analytical and numerical study. When the complete scan is done, BR(mu --> e, gamma) gets very insensitive to theta_13. Moreover, the values of the branching ratio are typically larger than those quoted in the literature, due to the large number of acceptable points in the parameter-space which were not considered before. Including (unflavoured) leptogenesis does not introduce any further dependence on theta_13, although decreases the typical value of BR(mu --> e, gamma).Comment: 22 pages, 5 figure

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic