Adaptive discrimination between harmful and harmless antigens in the immune system by predictive coding

なぜ免疫系はウイルスを排除して食べ物を排除しないのか？ --予測符号化に基づく免疫記憶のアップデート--. 京都大学プレスリリース. 2023-01-12.The immune system discriminates between harmful and harmless antigens based on past experiences; however, the underlying mechanism is largely unknown. From the viewpoint of machine learning, the learning system predicts the observation and updates the prediction based on prediction error, a process known as “predictive coding.” Here, we modeled the population dynamics of T cells by adopting the concept of predictive coding; conventional and regulatory T cells predict the antigen concentration and excessive immune response, respectively. Their prediction error signals, possibly via cytokines, induce their differentiation to memory T cells. Through numerical simulations, we found that the immune system identifies antigen risks depending on the concentration and input rapidness of the antigen. Further, our model reproduced history-dependent discrimination, as in allergy onset and subsequent therapy. Taken together, this study provided a novel framework to improve our understanding of how the immune system adaptively learns the risks of diverse antigens

Decoding reward–curiosity conflict in decision-making from irrational behaviors

機械学習により「心の揺れ・葛藤」の解読に成功 --報酬と好奇心の間で揺れる想い--. 京都大学プレスリリース. 2023-05-29.Humans and animals are not always rational. They not only rationally exploit rewards but also explore an environment owing to their curiosity. However, the mechanism of such curiosity-driven irrational behavior is largely unknown. Here, we developed a decision-making model for a two-choice task based on the free energy principle, which is a theory integrating recognition and action selection. The model describes irrational behaviors depending on the curiosity level. We also proposed a machine learning method to decode temporal curiosity from behavioral data. By applying it to rat behavioral data, we found that the rat had negative curiosity, reflecting conservative selection sticking to more certain options and that the level of curiosity was upregulated by the expected future information obtained from an uncertain environment. Our decoding approach can be a fundamental tool for identifying the neural basis for reward–curiosity conflicts. Furthermore, it could be effective in diagnosing mental disorders

Current status of a super-pressure balloon research of new design concept

A super-pressure balloon, which can reach the stratosphere with a heavy payload and continue to fly without ballasting, is quite useful for a long duration circum-polar flight. It has been quite difficult to develop such kind of balloons because of large pressure applied to the balloon film. The authors have investigated a new balloon design concept which reduces the film tension dramatically so as to enable the balloon to withstand high pressure. Experimental research has been proceeding to use the different size model balloons step by step. This report describes the current status of our research and development of the super-pressure balloon. The first successful flight test in the world for the balloon using this concept is also reported in this paper

Stem cell homeostasis regulated by hierarchy and neutral competition

幹細胞の栄枯盛衰のメカニズムを提唱 --多細胞組織における階層性と競争原理が織り成す幹細胞ダイナミクス--. 京都大学プレスリリース. 2022-12-15.Tissue stem cells maintain themselves through self-renewal while constantly supplying differentiating cells. Two distinct models have been proposed as mechanisms of stem cell homeostasis. According to the classical model, there is hierarchy among stem cells, and master stem cells produce stem cells by asymmetric division; whereas, according to the recent model, stem cells are equipotent and neutrally compete. However, the mechanism remains controversial in several tissues and species. Here, we developed a mathematical model linking the two models, named the hierarchical neutral competition (hNC) model. Our theoretical analysis showed that the combination of the hierarchy and neutral competition exhibited bursts in clonal expansion, which was consistent with experimental data of rhesus macaque hematopoiesis. Furthermore, the scaling law in clone size distribution, considered a unique characteristic of the recent model, was satisfied even in the hNC model. Based on the findings above, we proposed the criterion for distinguishing the three models based on experiments

Distinct predictive performance of Rac1 and Cdc42 in cell migration.

We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration

Stein Variational Guided Model Predictive Path Integral Control: Proposal and Experiments with Fast Maneuvering Vehicles

This paper presents a novel Stochastic Optimal Control (SOC) method based on Model Predictive Path Integral control (MPPI), named Stein Variational Guided MPPI (SVG-MPPI), designed to handle rapidly shifting multimodal optimal action distributions. While MPPI can find a Gaussian-approximated optimal action distribution in closed form, i.e., without iterative solution updates, it struggles with multimodality of the optimal distributions, such as those involving non-convex constraints for obstacle avoidance. This is due to the less representative nature of the Gaussian. To overcome this limitation, our method aims to identify a target mode of the optimal distribution and guide the solution to converge to fit it. In the proposed method, the target mode is roughly estimated using a modified Stein Variational Gradient Descent (SVGD) method and embedded into the MPPI algorithm to find a closed-form "mode-seeking" solution that covers only the target mode, thus preserving the fast convergence property of MPPI. Our simulation and real-world experimental results demonstrate that SVG-MPPI outperforms both the original MPPI and other state-of-the-art sampling-based SOC algorithms in terms of path-tracking and obstacle-avoidance capabilities. Source code: https://github.com/kohonda/proj-svg_mppiComment: 7 pages, 5 figure

Regulation of male germline transmission patterns by the Trp53-Cdkn1a pathway

A small number of offspring are born from the numerous sperm generated from spermatogonial stem cells (SSCs). However, little is known regarding the rules and molecular mechanisms that govern germline transmission patterns. Here we report that the Trp53 tumor suppressor gene limits germline genetic diversity via Cdkn1a. Trp53-deficient SSCs outcompeted wild-type (WT) SSCs and produced significantly more progeny after co-transplantation into infertile mice. Lentivirus-mediated transgenerational lineage analysis showed that offspring bearing the same virus integration were repeatedly born in a non-random pattern from WT SSCs. However, SSCs lacking Trp53 or Cdkn1a sired transgenic offspring in random patterns with increased genetic diversity. Apoptosis of KIT⁺ differentiating germ cells was reduced in Trp53- or Cdkn1a-deficient mice. Reduced CDKN1A expression in Trp53-deficient spermatogonia suggested that Cdkn1a limits genetic diversity by supporting apoptosis of syncytial spermatogonial clones. Therefore, the TRP53-CDKN1A pathway regulates tumorigenesis and the germline transmission pattern