AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Harmful Signaling in Matching Markets

Some labor markets have recently developed formal signaling mechanisms, e.g. the signaling for interviews in the job market for new Ph.D. economists. We evaluate the effect of such mechanisms on two-sided matching markets by considering a game of incomplete information between firms and workers. Workers have almost aligned preferences over firms: each worker has 'typical' commonly known preferences with probability close to one and 'atypical' idiosyncratic preferences with the complementary probability close to zero. Firms have commonly known preferences over workers. We show that the introduction of a signaling mechanism is harmful for this environment. Though signals transmit previously unavailable information, they also facilitate information asymmetry that leads to coordination failures. As a result, the introduction of a signaling mechanism lessens the expected number of matches when signals are informative

Hemodynamics in renal transplant in children with various morphological changes in the long-term post-transplant period

Introduction. Ultrasound scanning is one of the main methods of instrumental examination of patients after allogenic transplantation of kidney. The main reasons of dysfunction of the kidney transplant in long post-transplantation term are acute or chronic rejection, as well as acute and chronic nephrotoxicity of calcineurin inhibitors.Objective. Assessment of dopplerographic indicators of the blood flow throughout the transplanted kidney vessels in patients with preserved nitrogen excretion function under various morphological changes.Materials and methods. The study includes an analysis of the medical history of 98 children with end-stage chronic renal failure who underwent 98 allogeneic kidney transplants from a posthumous donor. There were analyzed the results of 185 percutaneous puncture biopsies and ultrasound studies of renal transplants. The analyzed data of morphological studies are divided into 4 groups. 1st group – there are no morphological changes affecting graft function. 2nd group – morphological signs of calcineurin toxicity. 3rd group – borderline damage of the graft. 4th group – acute and chronic graft rejection.Results and discussion. Indices of resistance and pulsation measured at the level of the renal artery and interlobular arteries tended to decrease in the kidneys with immunological influence and remained stable in other morphological groups. This means that, the higher the degree of hyalinosis of the arteries, the lower the indices of resistance and pulsation indices measured at the level of the common renal artery and interlobular arteries.Conclusions. The revealed tendency of a decrease in the values of the resistance index and the pulsation index at the level of the common renal artery of the interlobular arteries can be considered as one of the initial ultrasound signs that allow to speak of a decrease in the elasticity of the vascular wall. Normal indices of renal hemodynamics do not exclude the presence of pathological processes leading to graft dysfunction

On the equivalence between Bayesian and dominant strategy implementation: the case of correlated types

We consider general social choice environments with private values and correlated types. Each agent's matrix of conditional probabilities satisfies the full rank condition. We show that for any Bayesian incentive compatible mechanism there exists a dominant strategy incentive compatible mechanism that delivers the same interim expected utilities to all agents and generates at least the same social surplus. In addition, if there is a social alternative that is inferior to the other alternatives for all agents the dominant strategy incentive compatible mechanism matches exactly the social surplus. These results extend to environments with interdependent values satisfying the single crossing condition