Research in stability of periodic motions Quarterly progress report, 5 May - 4 Aug. 1966

Instability of periodic orbits in restricted and reduced three-body problems using mapping by fixed point metho

Families of Canonical Transformations by Hamilton-Jacobi-Poincar\'e equation. Application to Rotational and Orbital Motion

The Hamilton-Jacobi equation in the sense of Poincar\'e, i.e. formulated in the extended phase space and including regularization, is revisited building canonical transformations with the purpose of Hamiltonian reduction. We illustrate our approach dealing with orbital and attitude dynamics. Based on the use of Whittaker and Andoyer symplectic charts, for which all but one coordinates are cyclic in the Hamilton-Jacobi equation, we provide whole families of canonical transformations, among which one recognizes the familiar ones used in orbital and attitude dynamics. In addition, new canonical transformations are demonstrated.Comment: 21 page

Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin

Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival (p = 0.0045). MDR1/3435(C > T), which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS (p = 0.0578), response rate (p = 0.0782) and TTP (p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP (p = 0.0405) and PFS (p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients