Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue.

The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation

Non-catalytic bromination of benzene: a combined computational and experimental study

The non-catalytic bromination of benzene is shown experimentally to require high 5-14M concentrations of bromine in order to proceed at ambient temperatures to form predominantly bromobenzene, along with detectable (The non-catalytic bromination of benzene is shown experimentally to require high 5-14M concentrations of bromine in order to proceed at ambient temperatures to form predominantly bromobenzene, along with detectable (The non-catalytic bromination of benzene is shown experimentally to require high 5-14M concentrations of bromine in order to proceed at ambient temperatures to form predominantly bromobenzene, along with detectable

Finite Countermodel Based Verification for Program Transformation (A Case Study)

Both automatic program verification and program transformation are based on program analysis. In the past decade a number of approaches using various automatic general-purpose program transformation techniques (partial deduction, specialization, supercompilation) for verification of unreachability properties of computing systems were introduced and demonstrated. On the other hand, the semantics based unfold-fold program transformation methods pose themselves diverse kinds of reachability tasks and try to solve them, aiming at improving the semantics tree of the program being transformed. That means some general-purpose verification methods may be used for strengthening program transformation techniques. This paper considers the question how finite countermodels for safety verification method might be used in Turchin's supercompilation method. We extract a number of supercompilation sub-algorithms trying to solve reachability problems and demonstrate use of an external countermodel finder for solving some of the problems.Comment: In Proceedings VPT 2015, arXiv:1512.0221

Recursive Program Optimization Through Inductive Synthesis Proof Transformation

The research described in this paper involved developing transformation techniques which increase the efficiency of the noriginal program, the source, by transforming its synthesis proof into one, the target, which yields a computationally more efficient algorithm. We describe a working proof transformation system which, by exploiting the duality between mathematical induction and recursion, employs the novel strategy of optimizing recursive programs by transforming inductive proofs. We compare and contrast this approach with the more traditional approaches to program transformation, and highlight the benefits of proof transformation with regards to search, correctness, automatability and generality

An asymptotic theory for the re-equilibration of a micellar surfactant solution

Micellar surfactant solutions are characterized by a distribution of aggregates comprised predominantly of pre-micellar aggregates (monomers, dimers, trimers, etc.) and a region of proper micelles close to the peak aggregation number, connected by an intermediate region containing a very low concentration of aggregates. Such a distribution gives rise to a distinct two-timescale re-equilibration following a system dilution, known as the 1 and 2 processes, whose dynamics may be described by the Becker–Döring equations. We use a continuum version of these equations to develop a reduced asymptotic description that elucidates the behavior during each of these processes

Logical Step-Indexed Logical Relations

Appel and McAllester's "step-indexed" logical relations have proven to be a simple and effective technique for reasoning about programs in languages with semantically interesting types, such as general recursive types and general reference types. However, proofs using step-indexed models typically involve tedious, error-prone, and proof-obscuring step-index arithmetic, so it is important to develop clean, high-level, equational proof principles that avoid mention of step indices. In this paper, we show how to reason about binary step-indexed logical relations in an abstract and elegant way. Specifically, we define a logic LSLR, which is inspired by Plotkin and Abadi's logic for parametricity, but also supports recursively defined relations by means of the modal "later" operator from Appel, Melli\`es, Richards, and Vouillon's "very modal model" paper. We encode in LSLR a logical relation for reasoning relationally about programs in call-by-value System F extended with general recursive types. Using this logical relation, we derive a set of useful rules with which we can prove contextual equivalence and approximation results without counting steps