Activation of type II calcium/calmodulin-dependent protein kinase by Ca^(2+)/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain

It is now well established that autophosphorylation of a threonine residue located next to each calmodulin-binding domain in the subunits of type II Ca^(2+)/calmodulin-dependent protein kinase causes the kinase to remain active, although at a reduced rate, after Ca^(2+) is removed from the reaction. This autophosphorylated form of the kinase is still sensitive to Ca2+/calmodulin, which is required for a maximum catalytic rate. After removal of Ca^(2+), new sites are autophosphorylated by the partially active kinase. Autophosphorylation of these sites abolishes sensitivity of the kinase to Ca^(2+)/calmodulin (Hashimoto, Y., Schworer, C. M., Colbran, R. J., and Soderling, T. R. (1987) J. Biol. Chem. 262, 8051-8055). We have identified two pairs of homologous residues, Thr^(305) and Ser^(314) in the alpha subunit and Thr^(306) and Ser^(315) in the beta subunit, that are autophosphorylated only after removal of Ca^(2+) from an autophosphorylation reaction. The sites were identified by direct sequencing of labeled tryptic phosphopeptides isolated by reverse-phase high pressure liquid chromatography. Thr^(305-306) is rapidly dephosphorylated by purified protein phosphatases 1 and 2A, whereas Ser^(314-315) is resistant to dephosphorylation. We have shown by selective dephosphorylation that the presence of phosphate on Thr^(305-306) blocks sensitivity of the kinase to Ca^(2+)/calmodulin. In contrast, the presence of phosphate on Ser^(314-315) is associated with an increase in the Kact for Ca^(2+)/calmodulin of only about 2-fold, producing a relatively small decrease in sensitivity to Ca^(2+)/calmodulin

Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum.

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus

Strongly enhanced photon collection from diamond defect centres under micro-fabricated integrated solid immersion lenses

The efficiency of collecting photons from optically active defect centres in bulk diamond is greatly reduced by refraction and reflection at the diamond-air interface. We report on the fabrication and measurement of a geometrical solution to the problem; integrated solid immersion lenses (SILs) etched directly into the surface of diamond. An increase of a factor of 10 was observed in the saturated count-rate from a single negatively charged nitrogen-vacancy (NV-) within a 5um diameter SIL compared with NV-s under a planar surface in the same crystal. A factor of 3 reduction in background emission was also observed due to the reduced excitation volume with a SIL present. Such a system is potentially scalable and easily adaptable to other defect centres in bulk diamond.Comment: 5 Pages, 5 figures (4 subfigures) - corrected typ

Motion-base simulator study of control of an externally blown flap STOL transport aircraft after failure of an outboard engine during landing approach

A moving-base simulator investigation of the problems of recovery and landing of a STOL aircraft after failure of an outboard engine during final approach was made. The approaches were made at 75 knots along a 6 deg glide slope. The engine was failed at low altitude and the option to go around was not allowed. The aircraft was simulated with each of three control systems, and it had four high-bypass-ratio fan-jet engines exhausting against large triple-slotted wing flaps to produce additional lift. A virtual-image out-the-window television display of a simulated STOL airport was operating during part of the investigation. Also, a simple heads-up flight director display superimposed on the airport landing scene was used by the pilots to make some of the recoveries following an engine failure. The results of the study indicated that the variation in visual cues and/or motion cues had little effect on the outcome of a recovery, but they did have some effect on the pilot's response and control patterns

Thermal transistor: Heat flux switching and modulating

Thermal transistor is an efficient heat control device which can act as a heat switch as well as a heat modulator. In this paper, we study systematically one-dimensional and two-dimensional thermal transistors. In particular, we show how to improve significantly the efficiency of the one-dimensional thermal transistor. The study is also extended to the design of two-dimensional thermal transistor by coupling different anharmonic lattices such as the Frenkel-Kontorova and the Fermi-Pasta-Ulam lattices. Analogy between anharmonic lattices and single-walled carbon nanotube is drawn and possible experimental realization with multi-walled nanotube is suggested.Comment: To appear in J. Phys. Soc. Jp

Infrared catastrophe and tunneling into strongly correlated electron systems: Exact solution of the x-ray edge limit for the 1D electron gas and 2D Hall fluid

In previous work we have proposed that the non-Fermi-liquid spectral properties in a variety of low-dimensional and strongly correlated electron systems are caused by the infrared catastrophe, and we used an exact functional integral representation for the interacting Green's function to map the tunneling problem onto the x-ray edge problem, plus corrections. The corrections are caused by the recoil of the tunneling particle, and, in systems where the method is applicable, are not expected to change the qualitative form of the tunneling density of states (DOS). Qualitatively correct results were obtained for the DOS of the 1D electron gas and 2D Hall fluid when the corrections to the x-ray edge limit were neglected and when the corresponding Nozieres-De Dominicis integral equations were solved by resummation of a divergent perturbation series. Here we reexamine the x-ray edge limit for these two models by solving these integral equations exactly, finding the expected modifications of the DOS exponent in the 1D case but finding no changes in the DOS of the 2D Hall fluid with short-range interaction. We also provide, for the first time, an exact solution of the Nozieres-De Dominicis equation for the 2D electron gas in the lowest Landau level.Comment: 6 pages, Revte

What shapes a galaxy? - Unraveling the role of mass, environment and star formation in forming galactic structure

We investigate the dependence of galaxy structure on a variety of galactic and environmental parameters for ~500,000 galaxies at z<0.2, taken from the Sloan Digital Sky Survey data release 7 (SDSS-DR7). We utilise bulge-to-total stellar mass ratio, (B/T)_*, as the primary indicator of galactic structure, which circumvents issues of morphological dependence on waveband. We rank galaxy and environmental parameters in terms of how predictive they are of galaxy structure, using an artificial neural network approach. We find that distance from the star forming main sequence (Delta_SFR), followed by stellar mass (M_*), are the most closely connected parameters to (B/T)_*, and are significantly more predictive of galaxy structure than global star formation rate (SFR), or any environmental metric considered (for both central and satellite galaxies). Additionally, we make a detailed comparison to the Illustris hydrodynamical simulation and the LGalaxies semi-analytic model. In both simulations, we find a significant lack of bulge-dominated galaxies at a fixed stellar mass, compared to the SDSS. This result highlights a potentially serious problem in contemporary models of galaxy evolution.Comment: Accepted to MNRAS. 31 pages, 15 figure

Complexity-based learning and teaching: a case study in higher education

This paper presents a learning and teaching strategy based on complexity science and explores its impacts on a higher education game design course. The strategy aimed at generating conditions fostering individual and collective learning in educational complex adaptive systems, and led the design of the course through an iterative and adaptive process informed by evidence emerging from course dynamics. The data collected indicate that collaboration was initially challenging for students, but collective learning emerged as the course developed, positively affecting individual and team performance. Even though challenged, students felt highly motivated and enjoyed working on course activities. Their perception of progress and expertise were always high, and the academic performance was on average very good. The strategy fostered collaboration and allowed students and tutors to deal with complex situations requiring adaptation

A compilation, tabulation and analysis of spelling errors made by pupils in grades four, five, and six in free writing of sentences using given stimuli words

Thesis (M.A.)--Boston Universit