Given a Boolean formula F (X, Y), where X is a vector of outputs and Y is a vector of inputs, the Boolean functional synthesis problem requires us to compute a Skolem function vector Ψ(Y) for X such that F (Ψ(Y), Y) holds whenever ∃X F (X, Y) holds. In this paper, we investigate the relation between the representation of the specification F (X, Y) and the complexity of synthesis. We introduce a new normal form for Boolean formulas, called SynNNF, that guarantees polynomialtime synthesis and also polynomial-time existential quantification for some order of quantification of variables. We show that several normal forms studied in the knowledge compilation literature are subsumed by SynNNF, although SynNNF can be super-polynomially more succinct than them. Motivated by these results, we propose an algorithm to convert a specification in CNF to SynNNF, with the intent of solving the Boolean functional synthesis problem. Experiments with a prototype implementation show that this approach solves several benchmarks beyond the reach of state-of-the-art tools.• We present a new sub-class of negation normal form, called SynNNF, that admits polynomial-time synthesis and quantifier elimination for a set of variables.

Nutraceutical compounds show antioxidant and prooxidant properties under stress conditions like cancer, diabetes, and other diseases. The objective of this study is to find the dichotomic behavior of caffeine, curcumin, and naringenin on DNA of diabetic and normal subjects in the presence and absence of copper, hydrogen peroxide, and complex of copper-hydrogen peroxide. Hydrogen peroxide releases hydroxyl free radicals (•OH) on oxidation of Cu (I) to Cu (II) through Fenton-type reaction to cause DNA damage. In the results, agarose gel electrophoretic pattern speculates the prooxidant effect of caffeine and antioxidant effect of curcumin on DNA in the presence of copper and hydrogen peroxide. UV-Vis spectral analysis shows hyperchromism on addition of DNA to caffeine, hypochromism with curcumin, and subtle changes with naringenin. The chosen nutraceuticals act as inducers and quenchers of oxidative free radicals arising from diabetes.

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The small intestinal axis is a network of anatomical and functional connections linking the small intestine with the rest of the body. It senses external signals in the gut lumen and translates them into systemic immune effects. We have previously shown that an oral microbial drug candidate induces anti-inflammatory activity in preclinical models of inflammation by acting directly on host cells without colonization of the gut or modulation of the microbiome. We now extend these observations to EDP2939, a bacterial extracellular vesicle (EV), that has potent anti-inflammatory activity in preclinical models. EVs are non-replicating bacterial membrane vesicles with approximately 1/1000th the volume of the parent cell. EDP2939 was orally delivered and gut-restricted in distribution, it acts by modulation of innate and adaptive immunity within the small intestine to attenuate systemic inflammatory responses. We observed significantly decreased ear swelling and inflammation in a delayed-type hypersensitivity model, showing that EDP2939 modulates systemic inflammatory responses. Activity of EDP2939 is dependent upon both TLR2 signaling and the presence of local immune cells. In vitro results show TLR2 agonism and induction of anti-inflammatory cytokine responses in immune cells by EVs. This is the first report of striking anti-inflammatory effects of an orally delivered microbial extracellular vesicle. EDP2939 induces broad-based resolution of inflammation across multiple pathways via a novel mechanism of systemic pharmacology without systemic exposure. EVs are particularly effective at engaging host cells in the gut to modulate distal inflammation. These data point to oral EVs as a new class of immunotherapeutic drugs.