Stapled α-helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo. Specifically, ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities, shows submicromolar cellular activities in cancer cel...

Ejection chain methods, which include the classical Lin-Kernighan (LK) procedure and the Stem-and-Cycle (S&C) reference structure, have been the source of the currently leading algorithms for large scale symmetric traveling salesman problems (STSP). Although these methods proved highly effective in generating large neighborhoods for symmetric instances, their potential application to the asymme...

Penelitian ini bertujuan untuk mengetahui keselarasan arah kebijakan terhadap implementasi kerangka ASEAN Tourism Strategic Plan pada tatanan Pemerintah Daerah dalam pengembangan sektor pariwisata di Kabupaten Banyuwangi. Jenis pendekatan yang digunakan penelitian adalah deskriptif kualitatif dengan teknik analisis Miles and Huberman. Subjek dilibatkan mencakup elemen pentahelix objek inti berb...

We present deterministic approximation algorithms for the multi-criteria traveling salesman problem (TSP). Our algorithms are faster and simpler than the existing randomized algorithms. First, we devise algorithms for the symmetric and asymmetric multicriteria Max-TSP that achieve ratios of 1/2k − ε and 1/(4k − 2) − ε, respectively, where k is the number of objective functions. For two objectiv...

In this paper, we study the relationship between the Asymmetric Traveling Salesman Problem (ATSP) and the Cycle Cover Problem in terms of the strength of the triangle inequality on the edge costs in the given complete directed graph instance, G = (V, E). The strength of the triangle inequality is captured by parametrizing the triangle inequality as follows. A complete directed graph G = (V, E) ...

In this paper we contextualize, in terms of the ATSP, a recent compact formulation presented in Godinho et al (2010) for the time-dependent travelling salesman problem (TDTSP). The previous paper provides one way of viewing the new model, “the time-dependent TSP way” where it is put in evidence how to obtain the new model by tightening the linear programming relaxation of a well known formulati...

In metric asymmetric traveling salesperson problems the input is a complete directed graph in which edge weights satisfy the triangle inequality, and one is required to find a minimum weight walk that visits all vertices. In the asymmetric traveling salesperson problem (ATSP) the walk is required to be cyclic. In asymmetric traveling salesperson path problem (ATSPP), the walk is required to sta...

We study the approximation hardness of the Shortest Superstring, the Maximal Compression and the Maximum Asymmetric Traveling Salesperson (MAX-ATSP) problem. We introduce a new reduction method that produces strongly restricted instances of the Shortest Superstring problem, in which the maximal orbit size is eight (with no character appearing more than eight times) and all given strings having ...

In multi-criteria optimization problems, several objective functions have to be optimized. Since the different objective functions are usually in conflict with each other, one cannot consider only one particular solution as the optimal solution. Instead, the aim is to compute a so-called Pareto curve of solutions. Since Pareto curves cannot be computed efficiently in general, we have to be cont...