5,462 research outputs found

    Distinct forebrain and cerebellar isozymes of type II Ca^(2+)/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction

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    Forebrain and cerebellar Type II Ca2+/calmodulin-dependent protein kinases have different subunit compositions. The forebrain holoenzyme, characterized in our laboratory, is a 650-kDa holoenzyme composed of 50-kDa alpha-subunits and 60-kDa beta-subunits assembled in approximately a 3:1 ratio (Bennett, M. K., Erondu, N. E., and Kennedy, M. B. (1983) J. Biol. Chem. 258, 12735-12744). The cerebellar isozyme is a 500-kDa holoenzyme composed of alpha-subunits and beta-subunits assembled in almost the converse ratio, approximately four beta-subunits for each alpha-subunit. When compared by tryptic peptide mapping and by immunochemical techniques, the beta-subunits from the two brain regions are indistinguishable and the alpha-subunits appear closely related. The specific activities, substrate specificities, and catalytic constants of the cerebellar and forebrain isozymes are similar, suggesting that the alpha- and beta-subunits contain similar catalytic sites. However, two differences in the properties of the isozymes may result in functional differences between them in vivo. First, the apparent affinity of the cerebellar kinase for Ca2+/calmodulin is 2-fold higher than that of the forebrain kinase. Second, the two isozymes appear to associate differently with subcellular structures. Approximately 85% of the cerebellar kinase and 50% of the forebrain kinase remain in the particulate fraction after homogenization under standard conditions. However, they are present in different amounts in postsynaptic density fractions. Postsynaptic densities prepared from forebrain contain the forebrain isozyme. Immunochemical measurements show that it comprises approximately 16% of their total protein. In contrast, postsynaptic densities prepared from cerebellum contain the cerebellar isozyme, but it comprises only approximately 1-2% of their total protein. Thus, the alpha-subunit may play a role in anchoring Type II Ca2+/calmodulin-dependent protein kinase to postsynaptic densities

    Data Dilemmas in Forecasting European Office Market Rents

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    This paper uses data provided by three major real estate advisory firms to investigate the level and pattern of variation in the measurement of historic real estate rental values for the main European office centres. The paper assesses the extent to which the data providing organizations agree on historic market performance in terms of returns, risk and timing and examines the relationship between market maturity and agreement. The analysis suggests that at the aggregate level and for many markets, there is substantial agreement on direction, quantity and timing of market change. However, there is substantial variability in the level of agreement among cities. The paper also assesses whether the different data sets produce different explanatory models and market forecast. It is concluded that, although disagreement on the direction of market change is high for many market, the different data sets often produce similar explanatory models and predict similar relative performance.

    How Hot Is Radiation?

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    A self-consistent approach to nonequilibrium radiation temperature is introduced using the distribution of the energy over states. We begin rigorously with ensembles of Hilbert spaces and end with practical examples based mainly on the far from equilibrium radiation of lasers. We show that very high, but not infinite, laser radiation temperatures depend on intensity and frequency. Heuristic "temperatures" derived from a misapplication of equilibrium arguments are shown to be incorrect. More general conditions for the validity of nonequilibrium temperatures are also established.Comment: 26 pages, revised, LaTeX, 3 encapsulated PostScript figure

    Electromagnetically Inspired Approaches in Biomaterials and Drug Delivery

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    The ability to spatially and temporally regulate the delivery of therapeutic biomolecules in vivo is pervasively desired in contemporary and emerging biotechnological and therapeutic contexts. That is, because biology varies greatly in space and time, the medical community requires biomaterials and biosystems that can communicate/direct biology with a high degree of spatial and temporal precision. The ability to regulate the timing, dose, and directionality of multiple biomolecules is particularly desirable in the realm of tissue engineering, where the engineering/repair of functional tissues requires a highly choreographed sequence of localized biomolecular presentations. Here, I will describe works in progress towards the development of biomaterial systems—using simple electromagnetic principles as inspiration—that are capable of releasing molecular payloads in response to externally administered stimuli. I will describe how these systems may provide a high degree of control over the timing, dose, and directionality of multiple biomolecular presentations in wound healing and tissue engineering applications. I will also describe additional research directions geared towards directing biological processes that foundationally involve the use of electromagnetic principles. These projects will aim to (i) endow implant materials with bio-mimetic and bio-instructive properties, (ii) spatiotemporally regulate gene and drug delivery across cell membranes, and (iii) molecularly target undesirable cells for destruction

    Electromagnetically inspired biomaterials for directing biology

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    The ability to spatially and temporally regulate the delivery of biomolecules in vivo is pervasively desired in contemporary and emerging biotechnological and therapeutic contexts. The ability to regulate the timing, dose, and directionality of multiple biomolecules is particularly desirable in the realm of tissue engineering, where the engineering/repair of functional tissues requires a highly choreographed sequence of localized biomolecular presentations. Here, I will describe works in progress towards the development of biomaterial systems—using simple electromagnetic principles as inspiration—that are capable of releasing molecular payloads in response to externally administered stimuli. I will describe how these systems may provide a high degree of control over the timing, dose, and directionality of multiple biomolecular presentations in wound healing and tissue engineering applications. I will also describe additional research directions geared towards directing biological processes that foundationally involve the use of electromagnetic principles. These projects will aim to (i) endow implant materials with bio-mimetic and bio-instructive properties, (ii) spatiotemporally regulate gene and drug delivery across cell membranes, and (iii) molecularly target undesirable cells for destruction

    Zerronox Corporation: Using pulsed electron beams for the removal of carbon dioxide, nitrogen oxides and other emissions from power plants

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    Zerronox Corporation is a technology company addressing the market for emission abatement from fossil fuel power plants, specifically coal, natural gas, oil and diesel. Our mission is to commercialize the patented pulsed electron beam (PEB) technology for the cost effective removal of carbon dioxide, nitrogen oxides (NOx), and other exhaust stream pollutants such as sulfur oxides and mercury. The core technology was developed by the Naval Research Laboratory over the past fifteen years with a total investment from the DOE of more than $150M. Consequently, the developed technology is industrial scale in scope and has been tested for durability. The Company was formed to address the increasing emission standards promulgated by governmental regulatory agencies including the Clean Power Plan for CO2 , and the Regional Haze Rule, the Cross State Air Pollution Rule and the National Ambient Air Quality Standards for NOx. Today, conventional emission control processes are complex chemical operations that require heat, catalysts and reagents producing unusable by-products. Unlike these conventional emission abatement approaches, PEB uses physics rather than chemistry to break chemical bonds. In turn, there is no need for chemical reactions, high temperatures or catalysts. Consequently, capital and operational costs are approximately 5x-10x lower than the conventional removal technologies. The Zerronox PEB system uses two electron beam sources located on opposite sides of a continuous flow reaction chamber. These pulsed electron beams are generated by cathodes and emit symmetrically into a reaction chamber. Each pulse lasts for less than one millionth of a second, but produces hundreds of billions of watts of power for the conversion of emissions. As flue gas passes through the reaction chamber, the beam deposits its energy into the passing molecules, breaking their chemical bonds. There are many paths to leverage the PEB technology to reduce or convert carbon dioxide into useable products. Below are four possible processes. Four potential processes for CO2 abatement: First process: Use PEB to ionize CO2 to form CO2 + or CO2 + + Break CO2 + or CO2 + + apart using catalysts or reagents React with hydrogen or methane to form synfuels Second process: Use PEB to form either carbonates or hydrocarbons Will likely require salts, ammonia, urea or catalysts Third process: Use PEB to cluster CO2 to form (CO2) n Explore process using higher gas temperatures rather than condensation Store or dispose of solid (CO2) n by binding or coating with other chemicals Requires very low energy: plant power of \u3c5% Fourth process: Use PEB to convert coal to synfuels or marketable hydrocarbons The above processes are possible because modeling shows CO2 recombination after PEB is a relatively slow process (\u3e1 sec). We are estimating 5-10% of the plant’s power to remove 30-50% of carbon dioxide and 2% to 3% of the plant’s power to remove 80% of NOx, both of which are significantly lower cost alternatives than conventional emission removal technologies. Notably, the PEB system is modular in design that easily can be sized to meet the needs of any power company by merely building the required number of identical modules. In summary, Zerronox is well-positioned to become a leader in emission control systems. We have an experienced team of executives and engineers who are proven in developing technologies and scaling companies. Presently, a research program at the Naval Research Laboratory is ready to find solutions utilizing the pulsed electron beam approach that will be based on both theoretical and experimental plasma physics. We offer the power generation industry an opportunity to economically comply with ever-increasing regulations, while also improving air quality and mitigating the effects of greenhouse gases worldwide

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

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    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
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