The role of type 4 phosphodiesterases in generating microdomains of cAMP: Large scale stochastic simulations

Cyclic AMP (cAMP) and its main effector Protein Kinase A (PKA) are critical for several aspects of neuronal function including synaptic plasticity. Specificity of synaptic plasticity requires that cAMP activates PKA in a highly localized manner despite the speed with which cAMP diffuses. Two mechanisms have been proposed to produce localized elevations in cAMP, known as microdomains: impeded diffusion, and high phosphodiesterase (PDE) activity. This paper investigates the mechanism of localized cAMP signaling using a computational model of the biochemical network in the HEK293 cell, which is a subset of pathways involved in PKA-dependent synaptic plasticity. This biochemical network includes cAMP production, PKA activation, and cAMP degradation by PDE activity. The model is implemented in NeuroRD: novel, computationally efficient, stochastic reaction-diffusion software, and is constrained by intracellular cAMP dynamics that were determined experimentally by real-time imaging using an Epac-based FRET sensor (H30). The model reproduces the high concentration cAMP microdomain in the submembrane region, distinct from the lower concentration of cAMP in the cytosol. Simulations further demonstrate that generation of the cAMP microdomain requires a pool of PDE4D anchored in the cytosol and also requires PKA-mediated phosphorylation of PDE4D which increases its activity. The microdomain does not require impeded diffusion of cAMP, confirming that barriers are not required for microdomains. The simulations reported here further demonstrate the utility of the new stochastic reaction-diffusion algorithm for exploring signaling pathways in spatially complex structures such as neurons

Identifying galaxy candidates in WSRT HI imaging of ultra-compact high velocity clouds

Ultra-compact high velocity clouds (UCHVCs) were identified in the ALFALFA HI survey as potential gas-bearing dark matter halos. Here we present higher resolution neutral hydrogen (HI) observations of twelve UCHVCS with the Westerbork Synthesis Radio Telescope (WSRT). The UCHVCs were selected based on a combination of size, isolation, large recessional velocity and high column density as the best candidate dark matter halos. The WSRT data were tapered to image the UCHVCs at 210" (comparable to Arecibo) and 105" angular resolution. In a comparison of the single-dish to interferometer data, we find that the line flux recovered in the WSRT observations is comparable to that from the single-dish ALFALFA data. In addition, any structure seen in the ALFALFA data is reproduced in the WSRT maps at the same angular resolution. At 210'" resolution all the sources are generally compact with a smooth HI morphology, as expected from their identification as UCHVCs. At the higher angular resolution, a majority of the sources break into small clumps contained in a diffuse envelope. These UCHVCs also have no ordered velocity motion and are most likely Galactic halo clouds. We identify two UCHVCs, AGC 198606 and AGC 249525, as excellent galaxy candidates based on maintaining a smooth HI morphology at higher angular resolution and showing ordered velocity motion consistent with rotation. A third source, AGC 249565, lies between these two populations in properties and is a possible galaxy candidate. If interpreted as gas-bearing dark matter halos, the three candidate galaxies have rotation velocities of 8-15 km/s, HI masses of 0.6-50 x 10^5 Msun, HI radii of 0.3-2 kpc, and dynamical masses of 2-20 x 10^7 Msun for a range of plausible distances. These are the UCHVCs with the highest column density values in the ALFALFA HI data and we suggest this is the best way to identify further candidates.Comment: Accepted for publication in A&A. 26 pages, 19 figures, 5 table

Localizing gravitational wave sources with optical telescopes and combining electromagnetic and gravitational wave data

Neutron star binaries, which are among the most promising sources for the direct detection of gravitational waves (GW) by ground based detectors, are also potential electromagnetic (EM) emitters. Gravitational waves will provide a new window to observe these events and hopefully give us glimpses of new astrophysics. In this paper, we discuss how EM information of these events can considerably improve GW parameter estimation both in terms of accuracy and computational power requirement. And then in return how GW sky localization can help EM astronomers in follow-up studies of sources which did not yield any prompt emission. We discuss how both EM source information and GW source localization can be used in a framework of multi-messenger astronomy. We illustrate how the large error regions in GW sky localizations can be handled in conducting optical astronomy in the advance detector era. We show some preliminary results in the context of an array of optical telescopes called BlackGEM, dedicated for optical follow-up of GW triggers, that is being constructed in La Silla, Chile and is expected to operate concurrent to the advanced GW detectors.Comment: 8 pages, 8 figures, Proceeding for Sant Cugat Forum for Astrophysic

Mechanism of CDW-SDW Transition in One Dimension

The phase transition between charge- and spin-density-wave (CDW, SDW) phases is studied in the one-dimensional extended Hubbard model at half-filling. We discuss whether the transition can be described by the Gaussian and the spin-gap transitions under charge-spin separation, or by a direct CDW-SDW transition. We determine these phase boundaries by level crossings of excitation spectra which are identified according to discrete symmetries of wave functions. We conclude that the Gaussian and the spin-gap transitions take place separately from weak- to intermediate-coupling region. This means that the third phase exists between the CDW and the SDW states. Our results are also consistent with those of the strong-coupling perturbative expansion and of the direct evaluation of order parameters.Comment: 5 pages(REVTeX), 5 figures(EPS), 1 table, also available from http://wwwsoc.nacsis.ac.jp/jps/jpsj/1999/p68a/p68a42/p68a42h/p68a42h.htm

Lessons from the Play Observatory: re-imagining learning through film-making and transludic practices in children’s pandemic play

This article focuses on children’s play during the pandemic and how some young people responded with hybrid, playful media-making. The Play Observatory was an ESRC-funded project led by UCL and the University of Sheffield, inviting children to make contributions to a national collection of stories, texts and artefacts linked with their play during lockdown. The cultural material generated by children is an important post-pandemic legacy that allows us to argue for informal film-making as a legitimate literacy practice. Insights gained from children’s creative film and animation work inspire new approaches to learning with media described as transludic, in which the characteristics of playful and improvised media production processes are given time and space to unfold

Phase Diagram of One-Dimensional Extended Hubbard Model at Half Filling

We reexamine the ground-state phase diagram of the one-dimensional half-filled Hubbard model with on-site and nearest-neighbor repulsive interactions. We calculate second-order corrections to coupling constants in the g-ology to show that the bond-charge-density-wave (BCDW) phase exists for weak couplings in between the charge density wave (CDW) and spin density wave (SDW) phases. We find that the umklapp scattering of parallel-spin electrons destabilizes the BCDW state and gives rise to a bicritical point where the CDW-BCDW and SDW-BCDW continuous-transition lines merge into the CDW-SDW first-order transition line.Comment: 4 pages, 3 figure

Clues on the evolution of the Carina dwarf spheroidal galaxy from the color distribution of its red giant stars

The thin red giant branch (RGB) of the Carina dwarf spheroidal galaxy appears at first sight quite puzzling and seemingly in contrast with the presence of several distinct bursts of star formation. In this Letter, we provide a measurement of the color spread of red giant stars in Carina based on new BVI wide-field observations, and model the width of the RGB by means of synthetic color-magnitude diagrams. The measured color spread, Sigma{V-I}=0.021 +/- 0.005, is quite naturally accounted for by the star-formation history of the galaxy. The thin RGB appears to be essentially related to the limited age range of its dominant stellar populations, with no need for a metallicity dispersion at a given age. This result is relatively robust with respect to changes in the assumed age-metallicity relation, as long as the mean metallicity over the galaxy lifetime matches the observed value ([Fe/H] = -1.91 +/- 0.12 after correction for the age effects). This analysis of photometric data also sets some constraints on the chemical evolution of Carina by indicating that the chemical abundance of the interstellar medium in Carina remained low throughout each episode of star formation even though these episodes occurred over many Gyr.Comment: 4 pages, 3 figures, accepted for publication in the Astrophysical Journal Letter

The frequency and properties of young tidal dwarf galaxies in nearby gas-rich groups

We present high-resolution Giant Metrewave Radio Telescope (GMRT) HI observations and deep Canada-France-Hawaii Telescope (CFHT) optical imaging of two galaxy groups: NGC 4725/47 and NGC 3166/9. These data are part of a multi-wavelength unbiased survey of the gas-rich dwarf galaxy populations in three nearby interacting galaxy groups. The NGC 4725/47 group hosts two tidal knots and one dIrr. Both tidal knots are located within a prominent HI tidal tail, appear to have sufficient mass (M_gas~10^8 M_sol) to evolve into long-lived tidal dwarf galaxies (TDGs) and are fairly young in age. The NGC 3166/9 group contains a TDG candidate, AGC 208457, at least three dIrrs and four HI knots. Deep CFHT imaging confirms that the optical component of AGC 208457 is bluer -- with a 0.28 mag g-r colour -- and a few Gyr younger than its purported parent galaxies. Combining the results for these groups with those from the NGC 871/6/7 group reported earlier, we find that the HI properties, estimated stellar ages and baryonic content of the gas-rich dwarfs clearly distinguish tidal features from their classical counterparts. We optimistically identify four potentially long-lived tidal objects associated to three separate pairs of interacting galaxies, implying that TDGs are not readily produced during interaction events as suggested by some recent simulations. The tidal objects examined in this survey also appear to have a wider variety of properties than TDGs of similar mass formed in current simulations of interacting galaxies, which could be the result of pre- or post-formation environmental influences.Comment: 18 pages, 14 figures, accepted for publication in MNRA

Efficiency of dairy rations containing various quantities of grain

The dairy cow is particularly well adapted for consuming and utilizing large quantities of roughages, though she responds well to grain feeding. The relative quantities of roughage and grain that should be fed are usually determined by the physiologic effects and economic efficiencies of such rations when fed to dairy cattle. One would hardly expect high.producing cows to maintain a high yield when consuming roughage alone, because such a ration is so bulky that it prevents the intake of sufficient nutrients for maximum production. And yet, very good results have been obtained in certain areas by such a system of feeding. Then, too, the nutrients of roughage crops are usually produced at considerably less cost than those of grain crops (17) (3). Furthermore, rough. ages are more plentiful on most farms than grain crops, especially in recent years when there has been a marked increase in the production of hay and pasture crops at some sacrifice of grain production. Under these conditions the advisability of supplementing roughage rations with grain becomes a question of interest to dairy farmers