ELM triggering conditions for the integrated modeling of H-mode plasmas

Recent advances in the integrated modeling of ELMy H-mode plasmas are presented. A new model for the H-mode pedestal and for the triggering of ELMs predicts the height, width, and shape of the H-mode pedestal and the frequency and width of ELMs. The model for the pedestal and ELMs is used in the ASTRA integrated transport code to follow the time evolution of tokamak discharges from L-mode through the transition from L-mode to H-mode, with the formation of the H-mode pedestal, and, subsequently, to the triggering of ELMs. Turbulence driven by the ion temperature gradient mode, resistive ballooning mode, trapped electron mode, and electron temperature gradient mode contributes to the anomalous thermal transport at the plasma edge in this model. Formation of the pedestal and the L-H transition is the direct result of flow shear suppression of anomalous transport. The periodic ELM crashes are triggered by MHD instabilities. Two mechanisms for triggering ELMs are considered: ELMs are triggered by ballooning modes if the pressure gradient exceeds the ballooning threshold or by peeling modes if the edge current density exceeds the peeling mode threshold. The BALOO, DCON, and ELITE ideal MHD stability codes are used to derive a new parametric expression for the peeling-ballooning threshold. The new dependence for the peeling-ballooning threshold is implemented in the ASTRA transport code. Results of integrated modeling of DIII-D like discharges are presented and compared with experimental observations. The results from the ideal MHD stability codes are compared with results from the resistive MHD stability code NIMROD.Presented at the Workshop Electric Fields Structures and Relaxation in Edge Plasmas, Nice, France, October 26–27, 2004.     

Film Growth and Surface Roughness with Effective Fluctuating Covalent Bonds in Evaporating Aqueous Solution of Reactive Hydrophobic and Polar Groups: A Computer Simulation Model

Summary: A computer simulation model is proposed to study film growth and surface roughness in aqueous (A) solution of hydrophobic (H) and hydrophilic (P) groups on a simple three dimensional lattice of size with an adsorbing substrate. Each group is represented by a particle with appropriate characteristics occupying a unit cube (i.e., eight sites). The Metropolis algorithm is used to move each particle stochastically. The aqueous constituents are allowed to evaporate while the concentration of H and P is constant. Reactions proceed from the substrate and bonded particles can hop within a fluctuating bond length. The film thickness ( ) and its interface width ( ) are examined for hardcore and interacting particles for a range of temperature ( ). Simulation data show a rapid increase in and followed by its non‐monotonic growth and decay before reaching steady‐state and near equilibrium ( ) in asymptotic time step limit. The growth can be described by power laws, e.g., with a typical value of in initial time regime followed by at . For hardcore system, the equilibrium film thickness ( ) and surface roughness ( ) seem to scale linearly with the temperature, i.e., at low and at higher . For interacting functional groups in contrast, the long time (unsaturated) film thickness and surface roughness, and decay rapidly followed by a slow increase on raising the temperature.

Growth of the average film thickness at a temperature .     

Studies of peptide a- and b-type fragment ions using stable isotope labeling and integrated ion mobility/tandem mass spectrometry

The structures of peptide a- and b-type fragment ions were studied using synthetic peptides including a set of isomeric peptides, differing in the sequence location of an alanine residue labeled with ¹⁵N and uniformly with ¹³C. The pattern of isotope labeling of second-generation fragment ions derived via a _n and b _n ions (where n=4 or 5) suggested that these intermediates existed in part as macrocyclic structures, where alternative sites of ring opening gave rise to different linear forms whose simple cleavage might give rise to the observed final products. Similar conclusions were derived from combined ion mobility/tandem MS analyses where different fragmentation patterns were observed for isomeric a- or b-type ions that display different ion mobilities. These analyses were facilitated by a new approach to the processing of ion mobility/tandem MS data, from which distinct and separate product ion spectra are derived from ions that are incompletely separated by ion mobility. Finally, an example is provided of evidence for a macrocyclic structure for b _n ions where n=8 or 9.     

High‐Throughput Bioassays using “Dip‐and‐Go” Multiplexed Electrospray Mass Spectrometry

A multiplexed system based on inductive nanoelectrospray mass spectrometry (nESI‐MS) has been developed for high‐throughput screening (HTS) bioassays. This system combines inductive nESI and field amplification micro‐electrophoresis to achieve a “dip‐and‐go” sample loading and purification strategy that enables nESI‐MS based HTS assays in 96‐well microtiter plates. The combination of inductive nESI and micro‐electrophoresis makes it possible to perform efficient in situ separations and clean‐up of biological samples. The sensitivity of the system is such that quantitative analysis of peptides from 1–10 000 nm can be performed in a biological matrix. A prototype of the automation system has been developed to handle 12 samples (one row of a microtiter plate) at a time. The sample loading and electrophoretic clean‐up of biosamples can be done in parallel within 20 s followed by MS analysis at a rate of 1.3 to 3.5 s per sample. The system was used successfully for the quantitative analysis of BACE1‐catalyzed peptide hydrolysis, a prototypical HTS assay of relevance to drug discovery. IC₅₀ values for this system were in agreement with LC‐MS but recorded in times more than an order of magnitude shorter.     

Progranulin is expressed within motor neurons and promotes neuronal cell survival

Background

Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.

Results

In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.

Conclusion

Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.     

Matrix-assisted laser desorption/ionization-collision induced dissociation of poly(styrene)

Matrix-assisted laser desorption/ionization-collision induced dissociation (MALDI-CID) has been employed for the analysis of poly(styrene) in a tandem hybrid sector-time of flight instrument. Spectra are shown for adducts of poly(styrene) with copper and silver ions. The distributions of fragment ion peaks were found to be consistent from precursor ions containing both metal ions. It is shown how the masses of the end groups of the polymer may be inferred from the mass-to-charge ratios of two of the series of ion peaks that are seen in the MALDI-CID spectra. Mechanisms are proposed for the formation of some of the other series of ion peaks that are observed in the spectra.     

Analytical performance of a high-pressure radio frequency-only quadrupole collision cell with an axial field applied by using conical rods

The effect on triple-quadrupole performance of applying an axial field, in an rf-only quadrupole collision cell operated at pressures sufficiently high that collisional focusing is operating, has been investigated. The advantages of such cells have been shown previously to include increased transmission and much improved resolution in fragment ion spectra relative to the performance of collision cells operating at lower gas pressures. The disadvantages of high-pressure collision cells all derive from the relatively long transit times for the ions, which can be long relative to characteristic times for scanning the first mass filter (precursor ion selector) or for switching its setting in multiple reaction monitoring (MRM) cycles. The present work describes experiments on a high-pressure cell in which an axial field is created through use of conical rather than cylindrical or hyperbolic rods. In addition, results of computations of the electric fields within such a cell, and of ion trajectories through it, are presented. It is shown that application of axial fields of the order of 0. 1 V/cm can remove all hysteresis effects associated with the long ion transit times, and thus provide excellent performance in quantitation work using MRM, as well as in other scan modes. Furthermore, the advantages of collisional focusing in quadrupole collision cells are shown to be unimpaired by these low axial fields.     

Exotic decay in cerium isotopes

Half life for the emission of exotic clusters like ⁸Be, ¹²C, ¹⁶O, ²⁰Ne, ²⁴Mg and ²⁸Si are computed taking Coulomb and proximity potentials as interacting barrier and many of these are found well within the present upper limit of measurement. These results lie very close to those values reported by Shanmugam et al using their cubic plus Yukawa plus exponential model (CYEM). It is found that ¹²C and ¹⁶O emissions from ¹¹⁶Ce and ¹⁶O from ¹¹⁸Ce are most favorable for measurement (T _1/2<10¹⁰ s). Lowest half life time for ¹⁶O emission from ¹¹⁶Ce stress the role of doubly magic ¹⁰⁰Sn daughter in exotic decay. Geiger-Nuttall plots were studied for different clusters and are found to be linear. Inclusion of proximity potential will not produce much deviation to linear nature of Geiger-Nuttall plots. It is observed that neutron excess in the parent nuclei slow down the exotic decay process. These findings support the earlier observations of Gupta and collaborators using their preformed cluster model (PCM).     

A distal histidine mutant (H52Q) of yeast cytochrome c peroxidase catalyzes the oxidation of H(2)O(2) instead of its reduction

A H52Q variant of yeast cytochrome c peroxidase (CcP), in which the distal histidine is replaced by glutamine, catalyzes oxidation of H(2)O(2) instead of reduction. This redirection of catalytic action is detected by protein film voltammetry. In the presence of H(2)O(2), wild-type CcP, adsorbed on a graphite electrode, shows a strong catalytic reduction wave commencing at about 0.8V (pH 5.4); by contrast, H52Q does not exhibit this activity but instead shows a catalytic oxidation current at potentials in the region of 0.9 V. The oxidation current is partly suppressed in the presence of tetranitromethane (a superoxide scavenger) and is not observed for other mutants studied, including H52A. The only significant structural change in the H52Q variant is that the Q-52 side chain occupies the space vacated by the H-52 imidazole; specifically, the N-epsilon atom that is believed to transfer a proton and induce O--O cleavage is replaced, to within 0.75 A, by the carbamide-O. Thus, while the weakly basic amide functionality is unable to serve in the reorganization of bound H(2)O(2), it is able to facilitate its oxidation, most obviously by serving as a H-bond acceptor to assist formation of a labile superoxide intermediate.