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)

Modular Palladium Bipyrazoles for the Isomerization of Allylbenzenes - Mechanistic Considerations and Insights into Catalyst Design and Activity, Role of Solvent, and Additive Effects

The catalytic activity of novel bidentate N,N-chelated palladium complexes derived from electron excessive, backbone fused 3,3′-bipyrazoles in the selective isomerization of terminal arylpropenoids and 1-alkenes is described. The catalysts are easily modified by appropriate wing tip substitution, while maintaining the same bulky, rigid unreactive aliphatic backbone. Eleven novel palladium complexes with different electronic and steric properties were investigated. Their performance in the palladium(II)-catalyzed isomerization of a series of substituted allylbenzenes was evaluated in terms of electronic as well as steric effects. Besides the clear finding of a general trend towards higher catalyst activity with more electron-donating properties of the coordinated N,N-bidentate ligands, we found that the catalytic process strongly depends on the choice of solvents and additives. Extensive solvent screening revealed that reactions run best in a 2:1 toluene-methanol mixture, with the alcohol employed being a crucial factor in terms of electronic and steric factors. A reaction mechanism involving a hydride addition–elimination mechanism starting with a palladium hydride species generated in situ in alcoholic solutions, as corroborated by experiments using deuterium labeled allylbenzene, seems to be most likely. The proposed mechanism is also supported by the observed reaction rate orders of κobs[cat.]≈1 (0.94), κobs [substrate]=0.20→1.0 (t→∞) and κobs [methanol]=−0.51 for the isomerization of allylbenzene. Furthermore, the influence of acid and base, as well as the role of the halide coordinated to the catalyst, are discussed. The system catalyzes the isomerization of allylbenzenes very efficiently yielding high E:Z selectivities under very mild conditions (room temperature) and at low catalyst loadings of 1 mol% palladium even in unpurified solvents. The integrity and stability of the catalyst system were confirmed by multiple addition reaction cycles, successive filtration and isolation experiments, and the lack of palladium black formation

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

A System for Real-Time Interactive Analysis of Deep Learning Training

Performing diagnosis or exploratory analysis during the training of deep learning models is challenging but often necessary for making a sequence of decisions guided by the incremental observations. Currently available systems for this purpose are limited to monitoring only the logged data that must be specified before the training process starts. Each time a new information is desired, a cycle of stop-change-restart is required in the training process. These limitations make interactive exploration and diagnosis tasks difficult, imposing long tedious iterations during the model development. We present a new system that enables users to perform interactive queries on live processes generating real-time information that can be rendered in multiple formats on multiple surfaces in the form of several desired visualizations simultaneously. To achieve this, we model various exploratory inspection and diagnostic tasks for deep learning training processes as specifications for streams using a map-reduce paradigm with which many data scientists are already familiar. Our design achieves generality and extensibility by defining composable primitives which is a fundamentally different approach than is used by currently available systems. The open source implementation of our system is available as TensorWatch project at https://github.com/microsoft/tensorwatch.Comment: Accepted at ACM SIGCHI Symposium on Engineering Interactive Computing Systems (EICS 2019). Code available as TensorWatch project at https://github.com/microsoft/tensorwatc

Querying knowledge graphs in natural language.

Knowledge graphs are a powerful concept for querying large amounts of data. These knowledge graphs are typically enormous and are often not easily accessible to end-users because they require specialized knowledge in query languages such as SPARQL. Moreover, end-users need a deep understanding of the structure of the underlying data models often based on the Resource Description Framework (RDF). This drawback has led to the development of Question-Answering (QA) systems that enable end-users to express their information needs in natural language. While existing systems simplify user access, there is still room for improvement in the accuracy of these systems. In this paper we propose a new QA system for translating natural language questions into SPARQL queries. The key idea is to break up the translation process into 5 smaller, more manageable sub-tasks and use ensemble machine learning methods as well as Tree-LSTM-based neural network models to automatically learn and translate a natural language question into a SPARQL query. The performance of our proposed QA system is empirically evaluated using the two renowned benchmarks-the 7th Question Answering over Linked Data Challenge (QALD-7) and the Large-Scale Complex Question Answering Dataset (LC-QuAD). Experimental results show that our QA system outperforms the state-of-art systems by 15% on the QALD-7 dataset and by 48% on the LC-QuAD dataset, respectively. In addition, we make our source code available

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

A potential test of the CP properties and Majorana nature of neutrinos

The scattering of solar neutrinos on electrons may reveal their CP properties, which are particularly sensitive to their Majorana nature. The cross section is sensitive to the neutrino dipole moments through an interference of electro-magnetic and weak amplitudes. We show how future solar neutrino experiments with good angular resolution and low energy threshold, such as Hellaz, can be sensitive to the resulting azimuthal asymmetries in event number, and could therefore provide valuable information on the CP properties and the nature of the neutrinos, provided the solar magnetic field direction is fixed.Comment: 14 pages, 1 figure, eq. (19) corrected. Version to be publishe

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.

Neutrino oscillations and the effect of the finite lifetime of the neutrino source

We consider a neutrino source at rest and discuss a condition for the existence of neutrino oscillations which derives from the finite lifetime $\tau_S$ of the neutrino source particle. This condition is present if the neutrino source is a free particle such that its wave function is non-stationary. For a Gaussian wave function and with some simplifying assumptions, we study the modification of the usual oscillation probability stemming from $\tau_S$. In the present accelerator experiments the effect of $\tau_S$ can be neglected. We discuss some experimental situations where the source lifetime becomes relevant in the oscillation formula.Comment: 13 pages latex file with 2 figure