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

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

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

Techniques for measuring atmospheric aerosols at the High Resolution Fly's Eye experiment

We describe several techniques developed by the High Resolution Fly's Eye experiment for measuring aerosol vertical optical depth, aerosol horizontal attenuation length, and aerosol phase function. The techniques are based on measurements of side-scattered light generated by a steerable ultraviolet laser and collected by an optical detector designed to measure fluorescence light from cosmic-ray air showers. We also present a technique to cross-check the aerosol optical depth measurement using air showers observed in stereo. These methods can be used by future air fluorescence experiments.Comment: Accepted for publication in Astroparticle Physics Journal 16 pages, 9 figure

Object-oriented Technology for Compressor Simulation

An object-oriented basis for interdisciplinary compressor simulation can, in principle, overcome several barriers associated with the traditional structured (procedural) development approach. This paper presents the results of a research effort with the objective to explore the repercussions on design, analysis, and implementation of a compressor model in an object oriented (OO) language, and to examine the ability of the OO system design to accommodate computational fluid dynamics (CFD) code for compressor performance prediction. Three fundamental results are that: (1) the selection of the object oriented language is not the central issue; enhanced (interdisciplinary) analysis capability derives from a broader focus on object-oriented technology; (2) object-oriented designs will produce more effective and reusable computer programs when the technology is applied to issues involving complex system inter-relationships (more so than when addressing the complex physics of an isolated discipline); and (3) the concept of disposable prototypes is effective for exploratory research programs, but this requires organizations to have a commensurate long-term perspective. This work also suggests that interdisciplinary simulation can be effectively accomplished (over several levels of fidelity) with a mixed language treatment (i.e., FORTRAN-C++), reinforcing the notion the OO technology implementation into simulations is a 'journey' in which the syntax can, by design, continuously evolve

Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort

Background. Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence. Method. A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy. Results. The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia. Conclusions. Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course

Magnetic Fluctuations in a Charge Ordered State of the One-Dimensional Extended Hubbard Model with a Half-Filled Band

Magnetic properties in a charge ordered state are examined for the extended Hubbard model at half-filling. Magnetic excitations, magnetic susceptibilities and a nuclear spin relaxation rate are calculated with taking account of fluctuations around the mean-field solution. The relevance of the present results to the observation in the 1:1 organic conductors, (TTM-TTP)I$_3$, is discussed.Comment: 4 pages, 3 figures, to be published in J. Phys. Soc. Jpn. Vol.71 (2002) No.

Dwarf Cepheids in the Carina Dwarf Spheroidal Galaxy

We have discovered 20 dwarf Cepheids (DC) in the Carina dSph galaxy from the analysis of individual CCD images obtained for a deep photometric study of the system. These short-period pulsating variable stars are by far the most distant (~100 kpc) and faintest (V ~ 23.0) DCs known. The Carina DCs obey a well-defined period-luminosity relation, allowing us to readily distinguish between overtone and fundamental pulsators in nearly every case. Unlike RR Lyr stars, the pulsation mode turns out to be uncorrelated with light-curve shape, nor do the overtone pulsators tend towards shorter periods compared to the fundamental pulsators. Using the period-luminosity (PL) relations from Nemec et al. (1994 AJ, 108, 222) and McNamara (1995, AJ, 109, 1751), we derive (m-M)_0 = 20.06 +/- 0.12, for E(B-V) = 0.025 and [Fe/H] = -2.0, in good agreement with recent, independent estimates of the distance/reddening of Carina. The error reflects the uncertainties in the DC distance scale, and in the metallicity and reddening of Carina. The frequency of DCs among upper main sequence stars in Carina is approximately 3%. The ratio of dwarf Cepheids to RR Lyr stars in Carina is 0.13 +/- 0.10, though this result is highly sensitive to the star-formation history of Carina and the evolution of the Horizontal Branch. We discuss how DCs may be useful to search effectively for substructure in the Galactic halo out to Galactocentric distances of ~100 kpc.Comment: 20 pages of text, 7 figure

A Unified Near Infrared Spectral Classification Scheme for T Dwarfs

A revised near infrared classification scheme for T dwarfs is presented, based on and superseding prior schemes developed by Burgasser et al. and Geballe et al., and defined following the precepts of the MK Process. Drawing from two large spectroscopic libraries of T dwarfs identified largely in the Sloan Digital Sky Survey and the Two Micron All Sky Survey, nine primary spectral standards and five alternate standards spanning spectral types T0 to T8 are identified that match criteria of spectral character, brightness, absence of a resolved companion and accessibility from both northern and southern hemispheres. The classification of T dwarfs is formally made by the direct comparison of near infrared spectral data of equivalent resolution to the spectra of these standards. Alternately, we have redefined five key spectral indices measuring the strengths of the major H$_2$O and CH$_4$ bands in the 1-2.5 micron region that may be used as a proxy to direct spectral comparison. Two methods of determining T spectral type using these indices are outlined and yield equivalent results. These classifications are also equivalent to those from prior schemes, implying that no revision of existing spectral type trends is required. The one-dimensional scheme presented here provides a first step toward the observational characterization of the lowest luminosity brown dwarfs currently known. Future extensions to incorporate spectral variations arising from differences in photospheric dust content, gravity and metallicity are briefly discussed. A compendium of all currently known T dwarfs with updated classifications is presented.Comment: 52 pages, 11 figures; accepted for publication to Ap

The Amateur Sky Survey Mark III Project

The Amateur Sky Survey (TASS) is a loose confederation of amateur and professional astronomers. We describe the design and construction of our Mark III system, a set of wide-field drift-scan CCD cameras which monitor the celestial equator down to thirteenth magnitude in several passbands. We explain the methods by which images are gathered, processed, and reduced into lists of stellar positions and magnitudes. Over the period October, 1996, to November, 1998, we compiled a large database of photometric measurements. One of our results is the "tenxcat" catalog, which contains measurements on the standard Johnson-Cousins system for 367,241 stars; it contains links to the light curves of these stars as well.Comment: 20 pages, including 4 figures; additional JPEG files for Figures 1, 2. Submitted to PAS