Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle

Cancer cells utilize large amounts of ATP to sustain growth, relying primarily on non-oxidative, fermentative pathways for its production. In many types of cancers this leads, even in the presence of oxygen, to the secretion of carbon equivalents (usually in the form of lactate) in the cell’s surroundings, a feature known as the Warburg effect. While the molecular basis of this phenomenon are still to be elucidated, it is clear that the spilling of energy resources contributes to creating a peculiar microenvironment for tumors, possibly characterized by a degree of toxicity. This suggests that mechanisms for recycling the fermentation products (e.g. a lactate shuttle) may be active, effectively inducing a mutually beneficial metabolic coupling between aberrant and non-aberrant cells. Here we analyze this scenario through a large-scale in silico metabolic model of interacting human cells. By going beyond the cell-autonomous description, we show that elementary physico- chemical constraints indeed favor the establishment of such a coupling under very broad conditions. The characterization we obtained by tuning the aberrant cell’s demand for ATP, amino-acids and fatty acids and/or the imbalance in nutrient partitioning provides quantitative support to the idea that synergistic multi-cell effects play a central role in cancer sustainmen

How Quantum Computers Fail: Quantum Codes, Correlations in Physical Systems, and Noise Accumulation

The feasibility of computationally superior quantum computers is one of the most exciting and clear-cut scientific questions of our time. The question touches on fundamental issues regarding probability, physics, and computability, as well as on exciting problems in experimental physics, engineering, computer science, and mathematics. We propose three related directions towards a negative answer. The first is a conjecture about physical realizations of quantum codes, the second has to do with correlations in stochastic physical systems, and the third proposes a model for quantum evolutions when noise accumulates. The paper is dedicated to the memory of Itamar Pitowsky.Comment: 16 page

Randomized Control in Performance Analysis and Empirical Asset Pricing

The present article explores the application of randomized control techniques in empirical asset pricing and performance evaluation. It introduces geometric random walks, a class of Markov chain Monte Carlo methods, to construct flexible control groups in the form of random portfolios adhering to investor constraints. The sampling-based methods enable an exploration of the relationship between academically studied factor premia and performance in a practical setting. In an empirical application, the study assesses the potential to capture premias associated with size, value, quality, and momentum within a strongly constrained setup, exemplified by the investor guidelines of the MSCI Diversified Multifactor index. Additionally, the article highlights issues with the more traditional use case of random portfolios for drawing inferences in performance evaluation, showcasing challenges related to the intricacies of high-dimensional geometry.Comment: 57 pages, 7 figures, 2 table