Potential Use of Folate-polyethylene glycol (PEG)-Appended Dendrimer (G3) Conjugate with alpha-Cyclodextrin as DNA Carriers to Tumor Cells

We previously reported that polyamidoamine STARBURST dendrimer (generation 3, G3) (dendrimer) conjugate with alpha-cyclodextrin (alpha-CyD) having an average degree of substitution of 2.4 of alpha-CyD (alpha-CDE) provided remarkable aspects as novel carriers for DNA and siRNA. To develop novel alpha-CDE derivatives with tumor cell specificity, we prepared folate-appended alpha-CDEs (Fol-alpha-CDEs) and folate-polyethylene glycol (PEG)-appended alpha-CDEs (Fol-PalphaCs) with the various degrees of substitution of folate (DSF), and evaluated in vitro and in vivo gene transfer activity, cytotoxicity, cellular association and physicochemical properties. In vitro gene transfer activity of Fol-alpha-CDEs (G3, DSF 2, 5 or 7) was lower than that of α-CDE (G3) in KB cells, folate receptor (FR)-overexpressing cancer cells. Of the three Fol-PalphaCs (G3, DSF 2, 5 or 7), Fol-PalphaC (G3, DSF 5) had the highest gene transfer activity in KB cells. The activity of Fol-PalphaC (G3, DSF 5) was significantly higher than that of alpha-CDE (G3) in KB cells, but not in A549 cells, FR-negative cells. Negligible cytotoxicity of the pDNA complex with Fol-PalphaC (G3, DSF 5) was observed in KB cells or A549 cells up to a charge ratio of 100/1 (carrier/pDNA). The cellular association of the pDNA complex with Fol-PalphaC (G3, DSF 5) could be mediated by FR on KB cells, resulting in its efficient cellular uptake. Fol-PalphaC (G3, DSF 5) had higher binding affinity with folate binding protein (FBP) than alpha-CDE (G3), although the physicochemical properties of pDNA complex with Fol-PalphaC (G3, DSF 5) were almost comparable to that with alpha-CDE (G3), although the onset charge ratio and the compaction ability of Fol-PalphaC (G3, DSF 5) were slightly different. Fol-PalphaC (G3, DSF 5) tended to show higher gene transfer activity than alpha-CDE (G3) 12 h after intratumoral administration in mice. These results suggest that Fol-PalphaC (G3, DSF 5), not Fol-alpha-CDEs, could be potentially used as a FR-overexpressing cancer cell-selective DNA carrier

forall x: Calgary. An Introduction to Formal Logic

forall x: Calgary is a full-featured textbook on formal logic. It covers key notions of logic such as consequence and validity of arguments, the syntax of truth-functional propositional logic TFL and truth-table semantics, the syntax of first-order (predicate) logic FOL with identity (first-order interpretations), translating (formalizing) English in TFL and FOL, and Fitch-style natural deduction proof systems for both TFL and FOL. It also deals with some advanced topics such as truth-functional completeness and modal logic. Exercises with solutions are available. It is provided in PDF (for screen reading, printing, and a special version for dyslexics) and in LaTeX source code

Matching Logic

This paper presents matching logic, a first-order logic (FOL) variant for specifying and reasoning about structure by means of patterns and pattern matching. Its sentences, the patterns, are constructed using variables, symbols, connectives and quantifiers, but no difference is made between function and predicate symbols. In models, a pattern evaluates into a power-set domain (the set of values that match it), in contrast to FOL where functions and predicates map into a regular domain. Matching logic uniformly generalizes several logical frameworks important for program analysis, such as: propositional logic, algebraic specification, FOL with equality, modal logic, and separation logic. Patterns can specify separation requirements at any level in any program configuration, not only in the heaps or stores, without any special logical constructs for that: the very nature of pattern matching is that if two structures are matched as part of a pattern, then they can only be spatially separated. Like FOL, matching logic can also be translated into pure predicate logic with equality, at the same time admitting its own sound and complete proof system. A practical aspect of matching logic is that FOL reasoning with equality remains sound, so off-the-shelf provers and SMT solvers can be used for matching logic reasoning. Matching logic is particularly well-suited for reasoning about programs in programming languages that have an operational semantics, but it is not limited to this