Cytochrome P4501-inhibiting chemicals amplify aryl hydrocarbon receptor activation and IL-22 production in T helper 17 cells

The aryl hydrocarbon receptor (AHR)controls interleukin 22 production by T helper 17 cells (Th17). IL-22contributes to intestinalhomeostasis but has also been implicated inchronic inflammatory disorders and colorectal cancer, highlighting the need for appropriate regulation of IL-22 production. Upon activation, the AHR induces expression of cytochrome P4501 (CYP1) enzymes that in turn play an important feedback role that curtails the duration of AHR signaling by metabolizingAHRligands. Recently we described how agents that inhibit CYP1 function potentiate AHR signalingby disruptingmetabolic clearance of the endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ). In the present study, we investigated the immune-modulating effects of environmental pollutants such as polycyclic aromatic hydrocarbons on Th17 differentiation and IL-22 production. Using Th17 cells deficient in CYP1 enzymes (Cyp1a1/1a2/1b1-/-)we show that these chemicals potentiate AHR activation through inhibition of CYP1 enzymes which leads to increases in intracellular AHR agonists. Our findings demonstrate that IL-22 production by Th17 cellsis profoundly enhanced by impaired CYP1-function and strongly suggest that chemicals able to modify CYP1 function or expression may disrupt AHR-mediated immune regulation by altering the levels of endogenous AHR agonist(s)

Catch trials in force field learning influence adaptation and consolidation of human motor memory

Thereby, subjects usually adapt their reaching movements to force field perturbations induced by a robotic device. In this context, so-called catch trials, in which the disturbing forces are randomly turned off, are commonly used to detect after-effects of motor adaptation. However, catch trials also produce sudden large motor errors that might influence the motor adaptation and the consolidation process. Yet, the detailed influence of catch trials is far from clear. Thus, the aim of this study was to investigate the influence of catch trials on motor adaptation and consolidation in force field experiments. Therefore, 105 subjects adapted their reaching movements to robot-generated force fields. The test groups adapted their reaching movements to a force field A followed by learning a second interfering force field B before retest of A (ABA). The control groups were not exposed to force field B (AA). To examine the influence of diverse catch trial ratios, subjects received catch trials during force field adaptation with a probability of either 0, 10, 20, 30, or 40%, depending on the group. First, the results on motor adaptation revealed significant differences between the diverse catch trial ratio groups. With increasing amount of catch trials, the subjects\u27 motor performance decreased and subjects\u27 ability to accurately predict the force field—and therefore internal model formation—was impaired. Second, our results revealed that adapting with catch trials can influence the following consolidation process as indicated by a partial reduction to interference. Here, the optimal catch trial ratio was 30%. However, detection of consolidation seems to be biased by the applied measure of performance

Three-dimensional Models of Core-collapse Supernovae From Low-mass Progenitors With Implications for Crab

We present 3D full-sphere supernova simulations of non-rotating low-mass (~9 Msun) progenitors, covering the entire evolution from core collapse through bounce and shock revival, through shock breakout from the stellar surface, until fallback is completed several days later. We obtain low-energy explosions [~(0.5-1.0)x 10^{50} erg] of iron-core progenitors at the low-mass end of the core-collapse supernova (LMCCSN) domain and compare to a super-AGB (sAGB) progenitor with an oxygen-neon-magnesium core that collapses and explodes as electron-capture supernova (ECSN). The onset of the explosion in the LMCCSN models is modelled self-consistently using the Vertex-Prometheus code, whereas the ECSN explosion is modelled using parametric neutrino transport in the Prometheus-HOTB code, choosing different explosion energies in the range of previous self-consistent models. The sAGB and LMCCSN progenitors that share structural similarities have almost spherical explosions with little metal mixing into the hydrogen envelope. A LMCCSN with less 2nd dredge-up results in a highly asymmetric explosion. It shows efficient mixing and dramatic shock deceleration in the extended hydrogen envelope. Both properties allow fast nickel plumes to catch up with the shock, leading to extreme shock deformation and aspherical shock breakout. Fallback masses of <~5x10^{-3} Msun have no significant effects on the neutron star (NS) masses and kicks. The anisotropic fallback carries considerable angular momentum, however, and determines the spin of the newly-born NS. The LMCCSNe model with less 2nd dredge-up results in a hydrodynamic and neutrino-induced NS kick of >40 km/s and a NS spin period of ~30 ms, both not largely different from those of the Crab pulsar at birth.Comment: 47 pages, 27 figures, 6 tables; minor revisions, accepted by MNRA

Next-Generation EU DataGrid Data Management Services

We describe the architecture and initial implementation of the next-generation of Grid Data Management Middleware in the EU DataGrid (EDG) project. The new architecture stems out of our experience and the users requirements gathered during the two years of running our initial set of Grid Data Management Services. All of our new services are based on the Web Service technology paradigm, very much in line with the emerging Open Grid Services Architecture (OGSA). We have modularized our components and invested a great amount of effort towards a secure, extensible and robust service, starting from the design but also using a streamlined build and testing framework. Our service components are: Replica Location Service, Replica Metadata Service, Replica Optimization Service, Replica Subscription and high-level replica management. The service security infrastructure is fully GSI-enabled, hence compatible with the existing Globus Toolkit 2-based services; moreover, it allows for fine-grained authorization mechanisms that can be adjusted depending on the service semantics.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla,Ca, USA, March 2003 8 pages, LaTeX, the file contains all LaTeX sources - figures are in the directory "figures

Effects of neutrino oscillations and neutrino magnetic moments on elastic neutrino-electron scattering

We consider elastic antineutrino-electron scattering taking into account possible effects of neutrino masses and mixing and of neutrino magnetic moments and electric dipole moments. Having in mind antineutrinos produced in a nuclear reactor we compute, in particular, the weak-electromagnetic interference terms which are linear in the magnetic (electric dipole) moments and also in the neutrino masses. We show that these terms are, however, suppressed compared to the pure weak and electromagnetic cross section. We also comment upon the possibility of using the electromagnetic cross section to investigate neutrino oscillations.Comment: 12 pages, REVTEX file, no figures, submitted to Phys.Rev.

A diagrammatic treatment of neutrino oscillations

We present a covariant wave-packet approach to neutrino flavor transitions in vacuum. The approach is based on the technique of macroscopic Feynman diagrams describing the lepton number violating processes of production and absorption of virtual massive neutrinos at the macroscopically separated space-time regions ("source" and "detector"). Accordingly, the flavor transitions are a result of interference of the diagrams with neutrinos of different masses in the intermediate states. The statistically averaged probability of the process is representable as a multidimensional integral of the product of the factors which describe the differential flux density of massless neutrinos from the source, differential cross section of the neutrino interaction with the detector and a dimensionless factor responsible for the flavor transition. The conditions are analyzed under which the last factor can be treated as the flavor transition probability in the usual quantum-mechanical sense.Comment: 27 pages,7 figures, iopart class. Includes minor corrections made in proofs. References update

Optimization strategies for fast detection of positive selection on phylogenetic trees.

MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total).Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/. CONTACT: [email protected] or [email protected]

DIANA Scheduling Hierarchies for Optimizing Bulk Job Scheduling

The use of meta-schedulers for resource management in large-scale distributed systems often leads to a hierarchy of schedulers. In this paper, we discuss why existing meta-scheduling hierarchies are sometimes not sufficient for Grid systems due to their inability to re-organise jobs already scheduled locally. Such a job re-organisation is required to adapt to evolving loads which are common in heavily used Grid infrastructures. We propose a peer-to-peer scheduling model and evaluate it using case studies and mathematical modelling. We detail the DIANA (Data Intensive and Network Aware) scheduling algorithm and its queue management system for coping with the load distribution and for supporting bulk job scheduling. We demonstrate that such a system is beneficial for dynamic, distributed and self-organizing resource management and can assist in optimizing load or job distribution in complex Grid infrastructures.Comment: 8 pages, 9 figures. Presented at the 2nd IEEE Int Conference on eScience & Grid Computing. Amsterdam Netherlands, December 200