The simulation of ionospheric conditions for space vehicles

Plasma wind tunnel to simulate ionospheric conditions for space vehicle

Regulation of Epac by cAMP

The role of cAMP as a second messenger in cellular signalling is well established. In the eukaryotic cell the targets of cAMP are PKA, cyclic nucleotide gated ion channels and Epac. All these proteins have a cAMP-binding domain of same architecture in common. Its function is to bind cAMP and thereby sense the presence of cAMP. Binding of cAMP to this sensor domain is transformed into an altered property of the whole protein. In spite of the important role of cAMP in regulating cellular events, the knowledge on a molecular level of how cAMP binding is translated into protein action was limited so far. For a long time structural information was available only for cAMP-bound (i.e. active) cAMP-binding domains, but information of cAMP free (i.e. inactive) cAMP-binding domains was missing. We determined the cAMP free crystal structure of the regulatory region of Epac2 containing two cAMP-binding domains. The high conservation of both sequence and structure between Epac and PKA allows to compare these structures as representatives of the ligand bound and the ligand free state of cAMP-binding domains in general. From these analyses a general model was developed of how cAMP-binding is sensed by cAMP-binding domains. A relative small rearrangement of residues directly involved in cAMP binding is transduced to a reorientation of the C-terminal helical part of the cAMP-binding domain. The helices of the different classes of cAMP-regulated proteins have common features related to the rearrangements induced by cAMP and unique features to allow communication to the respective remote parts of the protein. By adaptation of the C-terminal helix to the individual requirements in the context of the regulated protein class, the cAMP-binding domain can be used as an universal switch unit. The critical importance of this helix for the regulation of PKA, CAP and cyclic nucleotide gated ion channels is described in the literature and was shown for Epac by various approaches in this thesis. In Epac the helix forms an interface interacting with the catalytic region. This interaction blocks the catalytic centre in the absence of cAMP. This binding and therefore the blockage is terminated after binding of cAMP. To complete the structural investigation, extensive biochemical analysis was undertaken. This confirmed already mentioned the importance of the C-terminal helix and corroborated the mechanism suggested for cAMP sensing. In addition, the requirements for productive cAMP-binding and activation were characterised. Thus, the action of Epac specific activators such as 8-pCPT-2-O-Me-cAMP can be explained. This analogue is able to activate Epac with higher efficiency than normal cAMP, but can neither activate nor inhibit PKA. These studies showed also that it is in principle possible to inhibit Epac with certain cAMP analogues. Based on these findings it should be possible to develop Epac specific inhibitors. This will allow the specific investigation of Epac mediated effects

Modeling and Analysis of Power Processing Systems

The feasibility of formulating a methodology for the modeling and analysis of aerospace electrical power processing systems is investigated. It is shown that a digital computer may be used in an interactive mode for the design, modeling, analysis, and comparison of power processing systems

Rapid distortion theory for differential diffusion

Rapid distortion theory (RDT) is used to examine differential diffusion of active and passive scalars in unsheared, initially isotropic turbulence. RDT is well suited to study differential diffusion because it applies to strongly stratified flows with weak turbulence—that is, the conditions under which differential diffusion occurs. The theory reproduces several key features of the evolution of scalar fluxes and scalar flux spectra observed in direct numerical simulations (DNS). Predictions of the diffusivity ratio match laboratory results well when a parameter of the theory is related to a parameter of the experiments. RDT also allows parameters such as molecular diffusivities to be varied over a wider range than DNS can currently reach. RDT may prove to be a useful tool for computing mixing in weakly turbulent parts of the stratified ocean interior and possibly for parameterizing subgrid scale mixing in general circulation models

Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1

Screening of a carefully selected library of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic nucleotide-binding domain (CNB) of the cAMP sensor, EPAC1. Two of these hits (I942 and I178) were selected for their robust and reproducible inhibitory effects within the primary screening assay. Follow-up characterisation by ligand observed nuclear magnetic resonance (NMR) revealed direct interaction of I942 and I178 with EPAC1 and EPAC2-CNBs in vitro. Moreover, in vitro guanine nucleotide exchange factor (GEF) assays revealed that I942 and, to a lesser extent, I178 had partial agonist properties towards EPAC1, leading to activation of EPAC1, in the absence of cAMP, and inhibition of GEF activity in the presence of cAMP. In contrast, there was very little agonist action of I942 towards EPAC2 or protein kinase A (PKA). To our knowledge, this is the first observation of non-cyclic-nucleotide small molecules with agonist properties towards EPAC1. Furthermore, the isoform selective agonist nature of these compounds highlights the potential for the development of small molecule tools that selectively up-regulate EPAC1 activity

Multi-kilowatt modularized spacecraft power processing system development

A review of existing information pertaining to spacecraft power processing systems and equipment was accomplished with a view towards applicability to the modularization of multi-kilowatt power processors. Power requirements for future spacecraft were determined from the NASA mission model-shuttle systems payload data study which provided the limits for modular power equipment capabilities. Three power processing systems were compared to evaluation criteria to select the system best suited for modularity. The shunt regulated direct energy transfer system was selected by this analysis for a conceptual design effort which produced equipment specifications, schematics, envelope drawings, and power module configurations

Buoyancy generated turbulence in stably stratified flow with shear

The energy evolution in buoyancy-generated turbulence subjected to shear depends on the gradient Richardson number Ri and the stratification number St, which is a ratio of the time scale of the initial buoyancy fluctuations to the time scale of the mean stratification. During an initial period, the flow state evolves as in the unsheared case. After this period, shear generates fluctuating velocity components for St=0.25, but it depletes the fluctuating vertical velocity component and temperature variance faster than in the unsheared case for St=4. Weak shear causes the kinetic and total energy to decrease faster than in the unsheared case, whereas strong shear adds more energy in comparison with the unsheared case. Energy increased with time in only one case considered (St=0.1 and Ri=0.04). When St\u3e1, the nonlinearity of the flow does not become significant even when Ri is small. Thus, results from rapid distortion theory and direct numerical simulation compare well. In particular, the theory reproduces trends in the energy evolution for St\u3e1

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio

Neutron dose rate at the SwissFEL injector test facility: first measurements

At the Paul Scherrer Institute, the new SwissFEL Free Electron Laser facility is currently in the design phase. It is foreseen to accelerate electrons up to a maximum energy of 7 GeV with a pulsed time structure. An injector test facility is operated at a maximum energy of 300 MeV and serves as the principal test and demonstration plant for the SwissFEL project. Secondary radiation is created in unavoidable interactions of the primary beam with beamline components. The resulting ambient dose-equivalent rate due to neutrons was measured along the beamline with different commercially available survey instruments. The present study compares the readings of these neutron detectors (one of them is specifically designed for measurements in pulsed fields). The experiments were carried out in both, a normal and a diagnostic mode of operation of the injecto

Structural and electrical transport properties of superconducting Au{0.7}In{0.3} films: A random array of superconductor-normal metal-superconductor (SNS) Josephson junctions

The structural and superconducting properties of Au{0.7}In{0.3} films, grown by interdiffusion of alternating Au and In layers, have been studied. The films were found to consist of a uniform solid solution of Au{0.9}In{0.1}, with excess In precipitated in the form of In-rich grains of various Au-In phases (with distinct atomic compositions), including intermetallic compounds. As the temperature was lowered, these individual grains became superconducting at a particular transition temperature (Tc), determined primarily by the atomic composition of the grain, before a fully superconducting state of zero resistance was established. From the observed onset Tc, it was inferred that up to three different superconducting phases could have formed in these Au{0.7}In{0.3} films, all of which were embedded in a uniform Au{0.9}In{0.1} matrix. Among these phases, the Tc of a particular one, 0.8 K, is higher than any previously reported for the Au-In system. The electrical transport properties were studied down to low temperatures. The transport results were found to be well correlated with those of the structural studies. The present work suggests that Au{0.7}In{0.3} can be modeled as a random array of superconductor-normal metal-superconductor (SNS) Josephson junctions. The effect of disorder and the nature of the superconducting transition in these Au{0.7}In{0.3} films are discussed.Comment: 8 text pages, 10 figures in one separate PDF file, submitted to PR