Role of plants in anticancer drug discovery

Cancer is one of the major causes of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Worldwide the alarming rise in mortality rate due to cancer has fuelled the pursuit for effective anticancer agents to combat this disease. Finding novel and efficient compounds of natural origin has been a major point of concern for research in the pharmaceutical sciences. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for cancer treatment. Many successful anti-cancer drugs currently in use or their analogues are plant derived and many more are under clinical trials. This review aims to highlight the invaluable role that plants have played, and continue to play, in the discovery of anticancer agents.We acknowledge the University of Pretoria for Postdoctoral fellowship to J.K. and B.A.M.http://www.elsevier.com/locate/phytolhb2017ChemistryGenetic

Efficient, mechanically-verified validation of satisfiability solvers

textSatisfiability (SAT) solvers are commonly used for a variety of applications, including hardware verification, software verification, theorem proving, debugging, and hard combinatorial problems. These applications rely on the efficiency and correctness of SAT solvers. When a problem is determined to be unsatisfiable, how can one be confident that a SAT solver has fully exhausted the search space? Traditionally, unsatisfiability results have been expressed using resolution or clausal proof systems. Resolution-based proofs contain perfect reconstruction information, but these proofs are extremely large and difficult to emit from a solver. Clausal proofs rely on rediscovery of inferences using a limited number of techniques, which typically takes several orders of magnitude longer than the solving time. Moreover, neither of these proof systems has been able to express contemporary solving techniques such as bounded variable addition. This combination of issues has left SAT solver authors unmotivated to produce proofs of unsatisfiability. The work from this dissertation focuses on validating satisfiability solver output in the unsatisfiability case. We developed a new clausal proof format called DRAT that facilitates compact proofs that are easier to emit and capable of expressing all contemporary solving and preprocessing techniques. Furthermore, we implemented a validation utility called DRAT-trim that is able to validate proofs in a time similar to that of the discovery time. The DRAT format has seen widespread adoption in the SAT community and the DRAT-trim utility was used to validate the results of the 2014 SAT Competition. DRAT-trim uses many advanced techniques to realize its performance gains, so why should the results of DRAT-trim be trusted? Mechanical verification enables users to model programs and algorithms and then prove their correctness with a proof assistant, such as ACL2. We designed a new modeling technique for ACL2 that combines efficient model execution with an agile and convenient theory. Finally, we used this new technique to construct a fast, mechanically-verified validation tool for proofs of unsatisfiability. This research allows SAT solver authors and users to have greater confidence in their results and applications by ensuring the validity of unsatisfiability results.Computer Science

Frying the Egg, Roasting the Chicken: Unit Deletions in DRAT Proofs

The final publication is available via https://doi.org/ 10.1145/3372885.3373821.The clausal proof format DRAT is the standard de facto to certify SAT solvers' unsatisfiability results. DRAT proofs act as logs of clause inferences and clause deletions in the solver. The non-monotonic nature of the proof system makes deletions relevant. State-of-the-art proof checkers ignore deletions of unit clauses, differing from the standard in meaningful ways that require adaptions when proofs are generated or used for purposes other than checking. On the other hand, dealing with unit deletions in the proof checker breaks many of the usual invariants used for efficiency reasons. Furthermore, many SAT solvers introduce spurious unit deletions in proofs. These deletions are never intended to be applied in the checker but are nevertheless introduced, making many proofs generated by state-of-the-art solvers incorrect. We present the first competitive DRAT checker that honors unit deletions, as well as fixes for the spurious deletion issue in proof generation. Our experimental results confirm that unit deletions can be applied with similar average performance to state-of-the-art checkers. We also confirm that a large fraction of the proofs generated during the last SAT solving competition do not respect the DRAT standard. This result was confirmed with proof incorrectness certificates that were independently validated. We find that our proof incorrectness certificates can be of help when debugging SAT solvers and DRAT checkers.Fonds zur Förderung der Wissenschaftlichen ForschungWiener Wissenschafts-, Forschungs- und Technologiefonds (WWTF