9,815 research outputs found

    Solving Tree Problems with Category Theory

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    Artificial Intelligence (AI) has long pursued models, theories, and techniques to imbue machines with human-like general intelligence. Yet even the currently predominant data-driven approaches in AI seem to be lacking humans' unique ability to solve wide ranges of problems. This situation begs the question of the existence of principles that underlie general problem-solving capabilities. We approach this question through the mathematical formulation of analogies across different problems and solutions. We focus in particular on problems that could be represented as tree-like structures. Most importantly, we adopt a category-theoretic approach in formalising tree problems as categories, and in proving the existence of equivalences across apparently unrelated problem domains. We prove the existence of a functor between the category of tree problems and the category of solutions. We also provide a weaker version of the functor by quantifying equivalences of problem categories using a metric on tree problems.Comment: 10 pages, 4 figures, International Conference on Artificial General Intelligence (AGI) 201

    A Strategy for Imidazotetrazine Prodrugs with Anti-cancer Activity Independent of MGMT and MMR

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    The imidazotetrazine ring is an acid-stable precursor and prodrug of highly-reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of temozolomide

    Role of the mesoamygdaloid dopamine projection in emotional learning

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    Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

    A facile method for bright, colour-tunable light-emitting diodes based on Ga-doped ZnO nanorods

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    © 2018 IOP Publishing Ltd. Bottom-up fabrication of nanowire-based devices is highly attractive for oxide photonic devices because of high light extraction efficiency; however, unsatisfactory electrical injection into ZnO and poor carrier transport properties of nanowires severely limit their practical applications. Here, we demonstrate that ZnO nanorods doped with Ga donors by in situ dopant incorporation during vapour-solid growth exhibit superior optoelectronic properties that exceed those currently synthesised by chemical vapour deposition, and accordingly can be electrically integrated into Si-based photonic devices. Significantly, the doping method was found to improve the nanorod quality by decreasing the concentration of point defects. Light-emitting diodes (LEDs) fabricated from the Ga-doped ZnO nanorod/p-Si heterojunction display bright and colour-tunable electroluminescence (EL). These nanorod LEDs possess a dramatically enhanced performance and an order of magnitude higher EL compared with equivalent devices fabricated with undoped nanorods. These results point to an effective route for large-scale fabrication of conductive, single-crystalline ZnO nanorods for photonic and optoelectronic applications

    Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

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    Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies

    DIAPHRAGM MUSCLE STRIP PREPARATION FOR EVALUATION OF GENE THERAPIES IN mdx MICE

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    1.  Duchenne muscular dystrophy (DMD), a severe muscle wasting disease of young boys with an incidence of one in every 3000, results from a mutation in the gene that encodes dystrophin. The absence of dystrophin expression in skeletal muscles and heart results in the degeneration of muscle fibres and, consequently, severe muscle weakness and wasting. The mdx mouse discovered in 1984, with some adjustments for differences, has proven to be an invaluable model for scientific investigations of dystrophy. 2.  The development of the diaphagm strip preparation provided an ideal experimental model for investigations of skeletal muscle impairments in structure and function induced by interactions of disease- and age-related factors. Unlike the limb muscles of the mdx mouse, which show adaptive changes in structure and function, the diaphragm strip preparation reflects accurately the deterioration in muscle structure and function observed in boys with DMD. 3.  The advent of sophisticated servo motors and force transducers interfaced with state-of-the-art software packages to drive complex experimental designs during the 1990s greatly enhanced the capability of the mdx mouse and the diaphragm strip preparation to evaluate more accurately the impact of the disease on the structure–function relationships throughout the life span of the mouse. 4.  Finally, during the 1990s and through the early years of the 21st century, many promising, sophisticated genetic techniques have been designed to ameliorate the devastating impact of muscular dystrophy on the structure and function of skeletal muscles. During this period of rapid development of promising genetic therapies, the combination of the mdx mouse and the diaphragm strip preparation has provided an ideal model for the evaluation of the success, or failure, of these genetic techniques to improve dystrophic muscle structure, function or both. With the 2 year life span of the mdx mouse, the impact of age-related effects can be studied in this model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72970/1/j.1440-1681.2007.04865.x.pd
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