Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context

The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds

Nonlocal QED admits a finitely induced gauge field action

The Letter reconsiders a result obtained by Chr\'etien and Peierls in 1954 within nonlocal QED in 4D [Proc. Roy. Soc. London A 223, 468]. Starting from secondly quantized fermions subject to a nonlocal action with the kernel $[ i\not\partial_x a(x) - m b(x)]$ and gauge covariantly coupled to an external U(1) gauge field they found that for $a = b$ the induced gauge field action cannot be made finite irrespectively of the choice of the nonlocality $a$ $(= b)$. But, the general case $a \neq b$ naturally to be studied admits a finitely induced gauge field action, as the present Letter demonstrates.Comment: 10 pages LATEX. Paper also available at http://links.jstor.org/sici?sici=0962-8444%2819951208%29451%3A1943%3C571%3ANQE AAF%3E2.0.CO%3B2-V; erratum at http://links.jstor.org/sici?sici=1364-5021%2819960608%29452%3A1949%3C1503%3AEN QEAA%3E2.0.CO%3B2-

Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro

Previous studies showed that γ-linolenic acid (GLA, 18: 3 ω-6), arachidonic acid (AA, 20:4 ω -6), eicosapentaenoic acid (EPA, 20: 5 ω -3) and docosahexaenoic acid (DHA, 22:6 ω -3) have selective tumoricidal action. In the present study, it was observed that dihomo-gamma-linolenic acid (DGLA) and AA, EPA and DHA have cytotoxic action on both vincristine-sensitive (KB-3-1) and resistant (KB-ChR-8-5) cancer cells in vitro that appeared to be a free-radical dependent process but not due to the formation of prostaglandins, leukotrienes and thromboxanes. Uptake of vincristine and fatty acids was higher while their efflux was lower in KB-3-1 cells compared with KB-ChR-8-5 cells, suggesting that drug resistant cells have an effective efflux pump. GLA, DGLA, AA, EPA and DHA enhanced the uptake and decreased efflux in both drug-sensitive and drug-resistant cells and augmented the susceptibility of tumor cells especially, of drug-resistant cells to the cytotoxic action of vincristine. These results suggest that certain polyunsaturated fatty acids have tumoricidal action and are capable of enhancing the cytotoxic action of anti-cancer drugs specifically, on drug-resistant cells by enhancing drug uptake and reducing its efflux. Thus, polyunsaturated fatty acids either by themselves or in combination with chemotherapeutic drugs have the potential as anti-cancer molecules

A Decidable Confluence Test for Cognitive Models in ACT-R

Computational cognitive modeling investigates human cognition by building detailed computational models for cognitive processes. Adaptive Control of Thought - Rational (ACT-R) is a rule-based cognitive architecture that offers a widely employed framework to build such models. There is a sound and complete embedding of ACT-R in Constraint Handling Rules (CHR). Therefore analysis techniques from CHR can be used to reason about computational properties of ACT-R models. For example, confluence is the property that a program yields the same result for the same input regardless of the rules that are applied. In ACT-R models, there are often cognitive processes that should always yield the same result while others e.g. implement strategies to solve a problem that could yield different results. In this paper, a decidable confluence criterion for ACT-R is presented. It allows to identify ACT-R rules that are not confluent. Thereby, the modeler can check if his model has the desired behavior. The sound and complete translation of ACT-R to CHR from prior work is used to come up with a suitable invariant-based confluence criterion from the CHR literature. Proper invariants for translated ACT-R models are identified and proven to be decidable. The presented method coincides with confluence of the original ACT-R models.Comment: To appear in Stefania Costantini, Enrico Franconi, William Van Woensel, Roman Kontchakov, Fariba Sadri, and Dumitru Roman: "Proceedings of RuleML+RR 2017". Springer LNC

Non-linear Group Actions with Polynomial Invariant Rings and a Structure Theorem for Modular Galois Extensions

Let $G$ be a finite $p$-group and $k$ a field of characteristic $p>0$. We show that $G$ has a \emph{non-linear} faithful action on a polynomial ring $U$ of dimension $n=\mathrm{log}_p(|G|)$ such that the invariant ring $U^G$ is also polynomial. This contrasts with the case of \emph{linear and graded} group actions with polynomial rings of invariants, where the classical theorem of Chevalley-Shephard-Todd and Serre requires $G$ to be generated by pseudo-reflections. Our result is part of a general theory of "trace surjective $G$-algebras", which, in the case of $p$-groups, coincide with the Galois ring-extensions in the sense of \cite{chr}. We consider the \emph{dehomogenized symmetric algebra} $D_k$, a polynomial ring with non-linear $G$-action, containing $U$ as a retract and we show that $D_k^G$ is a polynomial ring. Thus $U$ turns out to be \emph{universal} in the sense that every trace surjective $G$-algebra can be constructed from $U$ by "forming quotients and extending invariants". As a consequence we obtain a general structure theorem for Galois-extensions with given $p$-group as Galois group and any prescribed commutative $k$-algebra $R$ as invariant ring. This is a generalization of the Artin-Schreier-Witt theory of modular Galois field extensions of degree $p^s$.Comment: 20 page

Transmission protocols for instruction streams

Threads as considered in thread algebra model behaviours to be controlled by some execution environment: upon each action performed by a thread, a reply from its execution environment -- which takes the action as an instruction to be processed -- determines how the thread proceeds. In this paper, we are concerned with the case where the execution environment is remote: we describe and analyse some transmission protocols for passing instructions from a thread to a remote execution environment.Comment: 13 page

Towards a Generic Trace for Rule Based Constraint Reasoning

CHR is a very versatile programming language that allows programmers to declaratively specify constraint solvers. An important part of the development of such solvers is in their testing and debugging phases. Current CHR implementations support those phases by offering tracing facilities with limited information. In this report, we propose a new trace for CHR which contains enough information to analyze any aspects of \CHRv\ execution at some useful abstract level, common to several implementations. %a large family of rule based solvers. This approach is based on the idea of generic trace. Such a trace is formally defined as an extension of the $\omega_r^\lor$ semantics of CHR. We show that it can be derived form the SWI Prolog CHR trace

Security Policy Consistency

With the advent of wide security platforms able to express simultaneously all the policies comprising an organization's global security policy, the problem of inconsistencies within security policies become harder and more relevant. We have defined a tool based on the CHR language which is able to detect several types of inconsistencies within and between security policies and other specifications, namely workflow specifications. Although the problem of security conflicts has been addressed by several authors, to our knowledge none has addressed the general problem of security inconsistencies, on its several definitions and target specifications.Comment: To appear in the first CL2000 workshop on Rule-Based Constraint Reasoning and Programmin