The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, alpha(1)-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of (3)H-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4'-methoxybenzylamino, 3',4'-dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.

Pharmacological inhibitors of cyclin-dependent kinase (CDK)2 are currently in preclinical and clinical development. The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. A panel of guanine derivatives, including O 6

No abstract

Fig. 1. Predictive stepping and posture correction due to random force disturbances being applied to the body.Abstract. This paper describes the real-time modeling of 3D skeletal motion with balancing properties. Our goal is to mimic human responsiveness when external forces are applied to the model. To achieve this we use an inverted pendulum as a basis for achieving a self-balancing model. We demonstrate responsiveness in stepping and posture control via a simplified biped skeletal model using our technique.

Stroke commonly leads to partial or complete paralysis of one side of the body and there is limited availability of therapists to provide rehabilitation. It is a priority therefore to identify the most effective rehabilitation strategies and/or pharmacotherapies. Motor learning, the essential process underpinning rehabilitation, can be assessed more quickly and robustly than outcomes from rehabilitation. In this paper we describe a proof of concept system that utilises a bespoke video game to measure the critical components of motor learning. We demonstrate that it is sensitive enough to detect how simple changes in therapist instruction significantly change motor performance and learning. Although video games have been shown to aid in rehabilitation, this is the first time video games have been used to derive early response markers, based on the measurement of performance and motor learning, for use in the evaluation of the efficacy of a rehabilitation strategy.