Designing and Adapting Service-based Systems: A Service Discovery Framework

This chapter describes a service discovery framework that has been developed within the EU 6th Framework projects SeCSE and Gredia. The framework supports design of service-based systems based on existing services and adaptation of service based systems during their execution due to different situations. It assumes services described from different perspectives and uses complex service discovery queries specified in a XML-based language that we have developed. The work is illustrated with the Cell Phone Operator case study

Electrodynamics of Magnetars III: Pair Creation Processes in an Ultrastrong Magnetic Field and Particle Heating in a Dynamic Magnetosphere

We consider the details of the QED processes that create electron-positron pairs in magnetic fields approaching and exceeding 10^{14} G. The formation of free and bound pairs is addressed, and the importance of positronium dissociation by thermal X-rays is noted. We calculate the collision cross section between an X-ray and a gamma ray, and point out a resonance in the cross section when the gamma ray is close to the threshold for pair conversion. We also discuss how the pair creation rate in the open-field circuit and the outer magnetosphere can be strongly enhanced by instabilities near the light cylinder. When the current has a strong fluctuating component, a cascade develops. We examine the details of particle heating, and show that a high rate of pair creation can be sustained close to the star, but only if the spin period is shorter than several seconds. The dissipation rate in this turbulent state can easily accommodate the observed radio output of the transient radio-emitting magnetars, and even their infrared emission. Finally, we outline how a very high rate of pair creation on the open magnetic field lines can help to stabilize a static twist in the closed magnetosphere and to regulate the loss of magnetic helicity by reconnection at the light cylinder.Comment: 25 pages, submitted to the Astrophysical Journa

Genetic tracing of Ca(V)3.2 T-type calcium channel expression in the peripheral nervous system

Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus. In the peripheral nervous system, the activation of the promoter starts at E9.5 in neural crest cells that will give rise to dorsal root ganglia (DRG) neurons, but not sympathetic neurons. As development progresses the number of DRG cells expressing the Cav3.2 channel reaches around 7% of the DRG at E16.5, and remains constant until E18.5. Characterization of sensory neuron subpopulations at E18.5 showed that EGFP(+) cells are a heterogeneous population consisting mainly of TrkB(+) and TrkC(+) cells, while only a small percentage of DRG cells were TrkA(+). Genetic tracing of the sensory nerve end-organ innervation of the skin showed that the activity of the Cav3.2 channel promoter in sensory progenitors marks many mechanoreceptor and nociceptor endings, but spares slowly adapting mechanoreceptors with endings associated with Merkel cells. Our genetic analysis reveals for the first time that progenitors that express the Cav3.2 T-type calcium channel, defines a sensory specific lineage that populates a large proportion of the DRG. Using our Cav3.2-Cre mice together with AAV viruses containing a conditional fluorescent reporter (tdTomato) we could also show that Cre expression is largely restricted to two functionally distinct sensory neuron types in the adult ganglia. Cav3.2 positive neurons innervating the skin were found to only form lanceolate endings on hair follicles and are probably identical to D-hair receptors. A second population of nociceptive sensory neurons expressing the Cav3.2 gene was found to be positive for the calcitonin-gene related peptide but these neurons are deep tissue nociceptors that do not innervate the skin

Subunit-specific inhibition of acid sensing ion channels by stomatin-like protein 1

There are five mammalian stomatin-domain genes, all of which encode peripheral membrane proteins that can modulate ion channel function. Here we examined the ability of stomatin-like protein 1 (STOML1) to modulate the proton-sensitive members of the acid-sensing ion channel (ASIC) family. STOML1 profoundly inhibits ASIC1a, but has no effect on the splice variant ASIC1b. The inactivation time constant of ASIC3 is also accelerated by STOML1. We examined STOML1 null mutant mice with a β-galactosidase-neomycin cassette gene-trap reporter driven from the STOML1 gene locus, which indicated that STOML1 is expressed in at least 50% of dorsal root ganglion (DRG) neurones. Patch clamp recordings from mouse DRG neurones identified a trend for larger proton-gated currents in neurones lacking STOML1, which was due to a contribution of effects upon both transient and sustained currents, at different pH, a finding consistent with an endogenous inhibitory function for STOML1.This project was supported by grants of the German Research Council (SFB449/B18 and SFB958/A09 to G.R.L.)

Spin-Dependent Cyclotron Decay Rates in Strong Magnetic Fields

Cyclotron decay and absorption rates have been well studied in the literature, focusing primarily on spectral, angular and polarization dependence. Astrophysical applications usually do not require retention of information on the electron spin state, and these are normally averaged in obtaining the requisite rates. In magnetic fields, higher order quantum processes such as Compton scattering become resonant at the cyclotron frequency and its harmonics, with the resonances being formally divergent. Such divergences are usually eliminated by accounting for the finite lifetimes of excited Landau states. This practice requires the use of spin-dependent cyclotron rates in order to obtain accurate determinations of process rates very near cyclotronic resonances, the phase space domain most relevant for certain applications to pulsar models. This paper develops previous results in the literature to obtain compact analytic expressions for cyclotron decay rates/widths in terms of a series of Legendre functions of the second kind; these expressions can be expediently used in astrophysical models. The rates are derived using two popular eigenstate formalisms, namely that due to Sokolov and Ternov, and that due to Johnson and Lippmann. These constitute two sets of eigenfunctions of the Dirac equation that diagonalize different operators, and accordingly yield different spin-dependent cyclotron rates. This paper illustrates the attractive Lorentz transformation characteristics of the Sokolov and Ternov formulation, which is another reason why it is preferable when electron spin information must be explicitly retained.Comment: 11 pages, 2 embedded figures, apjgalley format, To appear in The Astrophysical Journal, Vol 630, September 1, 2005 issu

Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons

A complex of stomatin-family proteins and acid-sensing (proton-gated) ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates. Here, we have examined the role of the stomatin-family protein stomatin-like protein-3 (STOML3) in this process. We demonstrate that STOML3 interacts with stomatin and ASIC subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells. We identify a hydrophobic region in the N-terminus of STOML3 that is required for vesicular localization of STOML3 and regulates physical and functional interaction with ASICs. We further characterize STOML3-containing vesicles in DRG neurons and show that they are Rab11-positive, but not part of the early-endosomal, lysosomal or Rab14-dependent biosynthetic compartment. Moreover, uncoupling of vesicles from microtubules leads to incorporation of STOML3 into the plasma membrane and increased acid-gated currents. Thus, STOML3 defines a vesicle pool in which it associates with molecules that have critical roles in sensory transduction. We suggest that the molecular features of this vesicular pool may be characteristic of a ‘transducosome’ in sensory neurons

Alkaline Phosphatases: Structure, substrate specificity and functional relatedness to other members of a large superfamily of enzymes

Our knowledge of the structure and function of alkaline phosphatases has increased greatly in recent years. The crystal structure of the human placental isozyme has enabled us to probe salient features of the mammalian enzymes that differ from those of the bacterial enzymes. The availability of knockout mice deficient in each of the murine alkaline phosphatase isozymes has also given deep insights into their in vivo role. This has been particularly true for probing the biological role of bone alkaline phosphatase during skeletal mineralization. Due to space constraints this mini-review focuses exclusively on structural and functional features of mammalian alkaline phosphatases as identified by crystallography and probed by site-directed mutagenesis and kinetic analysis. An emphasis is also placed on the substrate specificity of alkaline phosphatases, their catalytic properties as phosphohydrolases as well as phosphodiesterases and their structural and functional relatedness to a large superfamily of enzymes that includes nucleotide pyrophosphatase/phosphodiesterase

Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type-specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype-specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type-dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function

DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds

A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)-regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals