Molecular modeling of tricyclic compounds with anilino substituents and their intercalation complexes with DNA sequences

Although 9-anilinoacridines are among the best studied antitumoral intercalators, there are few studies about the effect of isosteric substitution of a benzene moiety for a heterocycle ring in the acridine framework. According to these studies, this approach may lead to effective cytotoxic agents, but good cytotoxic activity depends on structural requirements in the aniline ring which differ from those in 9-anilinoacridines. The present paper deals with molecular modeling studies of some 9-anilino substituted tricyclic compounds and their intercalation complexes (in various DNA sequences) resulting from docking the compounds into various DNA sequences. As expected, the isosteric substitution in 9-anilinoacridines influences the LUMO energy values and orbital distribution, the dipole moment, electrostatic charges and the conformation of the anilino ring. Other important differences are observed during the docking studies, for example, changes in the spatial arrangement of the tricyclic nucleus and the anilino ring at the intercalation site. Semiempirical calculations of the intercalation complexes show that the isosteric replacement of a benzene ring in the acridine nucleus affects not only DNA affinity but also base pair selectivity. These findings explain, at least partially, the different structural requirements observed in several 9-anilino substituted tricyclic compounds for cytotoxic activity. Thus, the data presented here may guide the rational design of new agents with different DNA binding properties and/or a cytotoxic profile by isosteric substitution of known intercalators.     

An impulsive dynamical systems framework for reset control systems

Impulsive dynamical systems is a well-established area of dynamical systems theory, and it is used in this work to analyse several basic properties of reset control systems: existence and uniqueness of solutions, and continuous dependence on the initial condition (well-posedness). The work scope is about reset control systems with a linear and time-invariant base system, and a zero-crossing resetting law. A necessary and sufficient condition for existence and uniqueness of solutions, based on the well-posedness of reset instants, is developed. As a result, it is shown that reset control systems (with strictly proper plants) do not have Zeno solutions. It is also shown that full reset and partial reset (with a special structure) always produce well-posed reset instants. Moreover, a definition of continuous dependence on the initial condition is developed, and also a sufficient condition for reset control systems to satisfy that property. Finally, this property is used to analyse sensitivity of reset control systems to sensor noise. This work also includes a number of illustrative examples motivating the key concepts and main results.     

Computerized design of advanced straight and skew bevel gears produced by precision forging

The computerized design of advanced straight and skew bevel gears produced by precision forging is proposed. Modifications of the tooth surfaces of one of the members of the gear set are proposed in order to localize the bearing contact and predesign a favorable function of transmission errors. The proposed modifications of the tooth surfaces will be computed by using a modified imaginary crown-gear and applied in manufacturing through the use of the proper die geometry. The geometry of the die is obtained for each member of the gear set from their theoretical geometry obtained considering its generation by the corresponding imaginary crown-gear. Two types of surface modification, whole and partial crowning, are investigated in order to get the more effective way of surface modification of skew and straight bevel gears. A favorable function of transmission errors is predesigned to allow low levels of noise and vibration of the gear drive. Numerical examples of design of both skew and straight bevel gear drives are included to illustrate the advantages of the proposed geometry.     

An assessment of discretizations for convection-dominated convection–diffusion equations

The performance of several numerical schemes for discretizing convection-dominated convection–diffusion equations will be investigated with respect to accuracy and efficiency. Accuracy is considered in measures which are of interest in applications. The study includes an exponentially fitted finite volume scheme, the Streamline-Upwind Petrov–Galerkin (SUPG) finite element method, a spurious oscillations at layers diminishing (SOLD) finite element method, a finite element method with continuous interior penalty (CIP) stabilization, a discontinuous Galerkin (DG) finite element method, and a total variation diminishing finite element method (FEMTVD). A detailed assessment of the schemes based on the Hemker example will be presented.     

Random 3-SAT: The Plot Thickens

This paper presents an experimental investigation of the following questions: how does the average-case complexity of random 3-SAT, understood as a function of the order (number of variables) for fixed density (ratio of number of clauses to order) instances, depend on the density? Is there a phase transition in which the complexity shifts from polynomial to exponential in the order? Is the transition dependent or independent of the solver? Our experiment design uses three complete SAT solvers embodying different algorithms: GRASP, CPLEX, and CUDD. We observe new phase transitions for all three solvers, where the median running time shifts from polynomial in the order to exponential. The location of the phase transition appears to be solver-dependent. GRASP shifts from polynomial to exponential complexity near the density of 3.8, CPLEX shifts near density 3, while CUDD exhibits this transition between densities of 0.1 and 0.5. This experimental result underscores the dependence between the solver and the complexity phase transition, and challenges the widely held belief that random 3-SAT exhibits a phase transition in computational complexity very close to the crossover point.     

Event-driven,pattern-based methodology for cost-effective development of standardized personal health devices

Experiences applying standards in personal health devices (PHDs) show an inherent trade-off between interoperability and costs (in terms of processing load and development time). Therefore, reducing hardware and software costs as well as time-to-market is crucial for standards adoption. The ISO/IEEE11073 PHD family of standards (also referred to as X73PHD) provides interoperable communication between PHDs and aggregators. Nevertheless, the responsibility of achieving inexpensive implementations of X73PHD in limited resource microcontrollers falls directly on the developer. Hence, the authors previously presented a methodology based on patterns to implement X73-compliant PHDs into devices with low-voltage low-power constraints. That version was based on multitasking, which required additional features and resources. This paper therefore presents an event-driven evolution of the patterns-based methodology for cost-effective development of standardized PHDs. The results of comparing between the two versions showed that the mean values of decrease in memory consumption and cycles of latency are 11.59% and 45.95%, respectively. In addition, several enhancements in terms of cost-effectiveness and development time can be derived from the new version of the methodology. Therefore, the new approach could help in producing cost-effective X73-compliant PHDs, which in turn could foster the adoption of standards.     

Using OR to adapt supply chain management best practices to humanitarian logistics

The demand for humanitarian aid is extraordinarily large and it is increasing. In contrast, the funding for humanitarian operations does not seem to be increasing at the same rate. Humanitarian logistics has the challenge of allocating scarce resources to complex operations in an efficient way. After acquiring sufficient contextual knowledge, academics can use operations research (OR) to adapt successful supply chain management best practices to humanitarian logistics. We present two cases of OR applications to field vehicle fleet management in humanitarian operations. Our research shows that by using OR to adapt supply chain best practices to humanitarian logistics, significant improvements can be achieved.     

Deterministic planning in the fifth international planning competition: PDDL3 and experimental evaluation of the planners

The international planning competition (IPC) is an important driver for planning research. The general goals of the IPC include pushing the state of the art in planning technology by posing new scientific challenges, encouraging direct comparison of planning systems and techniques, developing and improving a common planning domain definition language, and designing new planning domains and problems for the research community. This paper focuses on the deterministic part of the fifth international planning competition (IPC5), presenting the language and benchmark domains that we developed for the competition, as well as a detailed experimental evaluation of the deterministic planners that entered IPC5, which helps to understand the state of the art in the field.We present an extension of pddl, called pddl3, allowing the user to express strong and soft constraints about the structure of the desired plans, as well as strong and soft problem goals. We discuss the expressive power of the new language focusing on the restricted version that was used in IPC5, for which we give some basic results about its compilability into pddl2. Moreover, we study the relative performance of the IPC5 planners in terms of solved problems, CPU time, and plan quality; we analyse their behaviour with respect to the winners of the previous competition; and we evaluate them in terms of their capability of dealing with soft goals and constraints, and of finding good quality plans in general. Overall, the results indicate significant progress in the field, but they also reveal that some important issues remain open and require further research, such as dealing with strong constraints and computing high quality plans in metric-time domains and domains involving soft goals or constraints.