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Optimization of a series of R132H IDH1 inhibitors from a high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in a xenograft model. Compound 35 shows good potency in the U87 R132H cell based assay and ∼90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. The magnitude and(More)
In bandit problems, a decision-maker must choose between a set of alternatives, each of which has a fixed but unknown rate of reward, to maximize their total number of rewards over a sequence of trials. Performing well in these problems requires balancing the need to search for highly-rewarding alternatives, with the need to capitalize on those alternatives(More)
Human subjects exhibit " sequential effects " in many psychological experiments, in which they respond more rapidly and accurately to a stimulus when it reinforces a local pattern in stimulus history, compared to when it violates such a pattern. This is often the case even if the local pattern arises by chance, such that stimulus history has no real(More)
Understanding how humans weigh long-term and short-term goals is important for both basic cognitive science and clinical neuroscience, as substance users need to balance the appeal of an immediate high vs. the long-term goal of sobriety. We use a computational model to identify learning and decision-making abnormalities in methamphetamine-dependent(More)
How humans achieve long-term goals in an uncertain environment, via repeated trials and noisy observations, is an important problem in cognitive science. We investigate this behavior in the context of a multi-armed bandit task. We compare human behavior to a variety of models that vary in their representational and computational complexity. Our result shows(More)
Diffusion models are widely-used and successful accounts of the time course of two-choice decision making. Most diffusion models assume constant boundaries, which are the threshold levels of evidence that must be sampled from a stimulus to reach a decision. We summarize theoretical results from statistics that relate distributions of decisions and response(More)
In The Price Is Right game show, players compete to win a prize, by placing bids on its price. We ask whether it is possible to achieve a "wisdom of the crowd" effect, by combining the bids to produce an aggregate price estimate that is superior to the estimates of individual players. Using data from the game show, we show that a wisdom of the crowd effect(More)