Identifying the effects of mechanical ventilation strategies and protocols in critical care requires analyzing data from heterogeneous patient-ventilator systems within the context of the clinical decision-making environment. This research develops a framework to help understand the consequences of mechanical ventilation (MV) and adjunct care decisions on patient outcome from observations of critical care patients receiving MV. Developing an understanding of and improving critical care respiratory management requires the analysis of existing secondary-use clinical data to generate hypotheses about advantageous variations and adaptations of current care. This work introduces a perspective of the joint patient-ventilator-care systems (so-called J6) to develop a scalable method for analyzing data and trajectories of these complex systems. To that end, breath behaviors are analyzed using evolutionary game theory (EGT), which generates the necessary quantitative precursors for deeper analysis through probabilistic and stochastic machinery such as reinforcement learning. This result is one step along the pathway toward MV optimization and personalization. The EGT-based process is analytically validated on synthetic data to reveal potential caveats before proceeding to real-world ICU data applications that expose complexities of the data-generating process J6. The discussion includes potential developments toward a state transition model for the simulating effects of MV decision using empirical and game-theoretic elements.

Accurate forecasting of infectious disease incidence is critical for public health planning and timely intervention. While most data-driven forecasting approaches rely primarily on historical data from a single country, such data are often limited in length and variability, restricting the performance of machine learning (ML) models. In this work, we investigate a cross-country learning approach for infectious disease forecasting, in which a single model is trained on time series data from multiple countries and evaluated on a country of interest. This setting enables the model to exploit shared epidemic dynamics across countries and to benefit from an enlarged training set. We examine this approach through a case study on COVID-19 case forecasting in Cyprus, using surveillance data from European countries. We evaluate multiple ML models and analyse the impact of the lookback window length and cross-country `data augmentation' on multi-step forecasting performance. Our results show that incorporating data from other countries can lead to consistent improvements over models trained solely on national data. Although the empirical focus is on Cyprus and COVID-19, the proposed framework and findings are applicable to infectious disease forecasting more broadly, particularly in settings with limited national historical data.

Reconstructing dynamical evolution from limited observations is a fundamental challenge in single-cell biology, where dynamic unbalanced optimal transport provides a principled framework for modeling coupled transport and mass variation. However, existing approaches rely on trajectory simulation at inference time, making inference a key bottleneck for scalable applications. In this work, we propose a mean-flow framework for unbalanced flow matching that summarizes both transport and mass-growth dynamics over arbitrary time intervals using mean velocity and mass-growth fields, enabling fast one-step generation without trajectory simulation. To solve dynamic unbalanced optimal transport under the Wasserstein-Fisher-Rao geometry, we further build on this framework to develop Wasserstein-Fisher-Rao Mean Flow Matching (WFR-MFM). Across synthetic and real single-cell RNA sequencing datasets, WFR-MFM achieves orders-of-magnitude faster inference than a range of existing baselines while maintaining high predictive accuracy, and enables efficient perturbation response prediction on large synthetic datasets with thousands of conditions.

Enabling natural communication through brain-computer interfaces (BCIs) remains one of the most profound challenges in neuroscience and neurotechnology. While existing frameworks offer partial solutions, they are constrained by oversimplified semantic representations and a lack of interpretability. To overcome these limitations, we introduce Semantic Intent Decoding (SID), a novel framework that translates neural activity into natural language by modeling meaning as a flexible set of compositional semantic units. SID is built on three core principles: semantic compositionality, continuity and expandability of semantic space, and fidelity in reconstruction. We present BrainMosaic, a deep learning architecture implementing SID. BrainMosaic decodes multiple semantic units from EEG/SEEG signals using set matching and then reconstructs coherent sentences through semantic-guided reconstruction. This approach moves beyond traditional pipelines that rely on fixed-class classification or unconstrained generation, enabling a more interpretable and expressive communication paradigm. Extensive experiments on multilingual EEG and clinical SEEG datasets demonstrate that SID and BrainMosaic offer substantial advantages over existing frameworks, paving the way for natural and effective BCI-mediated communication.

The spatial structure of populations may promote the emergence and maintenance of cooperation. Cooperation in the prisoner's dilemma is favored under specific update rules in evolutionary graph theory models with one individual per node of a graph, but this effect vanishes in models with well-mixed demes connected by migrations under soft selection. In contrast, experiments and models involving cycles of growth, merging and dilution have shown that spatial structure can favor cooperation. Here, we reconcile these findings by studying deme-structured populations under growth-merging-dilution dynamics, corresponding to a clique (fully connected graph) under hard selection. We obtain analytical conditions for the cooperator fraction to increase during deterministic logistic growth, and to increase on average under dilution-growth-merging cycles, in the weak selection regime. Furthermore, we analytically express the fixation probability of cooperators under weak selection, yielding a criterion for cooperative mutants to have a higher fixation probability than neutral ones. Finally, numerical simulations show that stochastic growth further promotes cooperation. Overall, hard selection is essential for cooperation to be promoted in deme-structured populations.

Each T cell typically carries a specific T-cell receptor (TCR) that determines its specificity against an epitope presented by the HLA complex on a target cell. Antigenic challenge triggers the expansion of reactive cells within a diverse pool of T cells with randomly generated receptors, a process that results in epitope-driven shifts of TCR frequencies over time. Here, we analyze the effects of SARS-CoV-2 vaccination on the TCR populations in peripheral blood drawn from seven COVID-naive individuals, before vaccines were widely available. To identify SARS-CoV-2 vaccine-associated TCR sequences among the $\sim 10^{5}-10^{6}$ TCR sequences sampled before and after vaccination, we develop statistical criteria to detect significant increases in abundance of positive TCR clones. Application of our statistical methods shows a robust identification of TCR sequences that respond to SARS-CoV-2 vaccination in vivo, illustrating the feasibility of quantifying the clone-specific dynamics of T-cell abundance changes following immunological perturbations.

Significance: Voltage imaging microscopy has emerged as a powerful tool to investigate neural activity both in vivo and in vitro. Various imaging approaches have been developed, including point-scanning, line-scanning and wide-field microscopes, however the effects of their different temporal sampling methods on signal fidelity have not yet been fully investigated. Aim: To provide an analysis of the inherent advantages and disadvantages of temporal sampling in scanning and wide-field microscopes and their effect on the fidelity of voltage spike detection. Approach: We develop a mathematical framework based on a mixture of analytical modeling and computer simulations with Monte-Carlo approaches. Results: Scanning microscopes outperform wide-field microscopes in low signal-to-noise conditions and when only a small subset of spikes needs to be detected. Wide-field microscopes outperform scanning microscopes when the measurement is temporally undersampled and a large fraction of the spikes needs to be detected. Both modalities converge in performance as sampling increases and the frame rate reaches the decay rate of the voltage indicator. Conclusions: Our work provides guidance for the selection of optimal temporal sampling parameters for voltage imaging. Most importantly it advises against using scanning voltage imaging microscopes at frame rates below 500 Hz.

This paper gives an overview of the use of control systems engineering in synthetic biology, motivated by applications such as cell therapy and cell fate reprogramming for regenerative medicine. A ubiquitous problem in these and other applications is the ability to control the concentration of specific regulatory factors in the cell accurately despite environmental uncertainty and perturbations. The paper describes the origin of these perturbations and how they affect the dynamics of the biomolecular ``plant'' to be controlled. A variety of biomolecular control implementations are then introduced to achieve robustness of the plant's output to perturbations and are grouped into feedback and feedforward control architectures. Although sophisticated control laws can be implemented in a computer today, they cannot be necessarily implemented inside the cell via biomolecular processes. This fact constraints the set of feasible control laws to those realizable through biomolecular processes that can be engineered with synthetic biology. After reviewing biomolecular feedback and feedforward control implementations, mostly focusing on the author's own work, the paper illustrates the application of such control strategies to cell fate reprogramming. Within this context, a master regulatory factor needs to be controlled at a specific level inside the cell in order to reprogram skin cells to pluripotent stem cells. The article closes by highlighting on-going challenges and directions of future research for biomolecular control design.

While businesses are typically more profitable if their workers and communities are minimally exposed to diseases, the same is not true for daycare centers. Here it is shown that a daycare center could maximize its profits by maintaining a population of sick children within the center, with the intention to infect more children who then do not attend. Through a modification of the Susceptible-Infected-Recovered (SIR) model for disease spread we find the optimal number of sick children who should be kept within the center to maximize profits. We show that as disease infectiousness increases, the optimal attendance rate of sick children approaches zero, while the potential profit increases.

Diffusion MRI (dMRI) tractography is currently the only method for in vivo mapping of the brain's white matter (WM) connections. Tractometry is an advanced tractography analysis technique for along-tract profiling to investigate the morphology and microstructural properties along the fiber tracts. Tractometry has become an essential tool for studying local along-tract differences between different populations (e.g., health vs disease). In this study, we propose a novel atlas-guided fine-scale tractometry method, namely AGFS-Tractometry, that leverages tract spatial information and permutation testing to enhance the along-tract statistical analysis between populations. There are two major contributions in AGFS-Tractometry. First, we create a novel atlas-guided tract profiling template that enables consistent, fine-scale, along-tract parcellation of subject-specific fiber tracts. Second, we propose a novel nonparametric permutation testing group comparison method to enable simultaneous analysis across all along-tract parcels while correcting for multiple comparisons. We perform experimental evaluations on synthetic datasets with known group differences and in vivo real data. We compare AGFS-Tractometry with two state-of-the-art tractometry methods, including Automated Fiber-tract Quantification (AFQ) and BUndle ANalytics (BUAN). Our results show that the proposed AGFS-Tractometry obtains enhanced sensitivity and specificity in detecting local WM differences. In the real data analysis experiments, AGFS-Tractometry can identify more regions with significant differences, which are anatomically consistent with the existing literature. Overall, these demonstrate the ability of AGFS-Tractometry to detect subtle or spatially localized WM group-level differences. The created tract profiling template and related code are available at: https://github.com/ZhengRuixi/AGFS-Tractometry.git.

Gas transport across cell membrane is a very important process in biochemistry which is essential for many crucial tasks, including cell respiration pH regulation in the cell. In the late 1990's, the suggestion that gasses are transported via preferred gas channels embedded into the cell membrane challenged the century old Overton's theory that gases pass through the lipid cell membrane by diffusing across the concentration gradient. Since experimental evidence alone does not provide enough evidence to favor one of the proposed mechanisms, mathematical models have been introduced to provide a context for the interpretation of laboratory measurement. Following up on previous work where the membrane permeability was estimated using particle filter, in this article we propose an algorithm based on dictionary learning for estimating cell membrane permeability. Computed examples illustrate that the novel approach, which can be applied when the properties of the membrane do not change in the course of the data collection process, is computationally much more efficient than particle filter.

Text-based foundation models have become an important part of scientific discovery, with molecular foundation models accelerating advancements in material science and molecular design.However, existing models are constrained by closed-vocabulary tokenizers that capture only a fraction of molecular space. In this work, we systematically evaluate 34 tokenizers, including 19 chemistry-specific ones, and reveal significant gaps in their coverage of the SMILES molecular representation. To assess the impact of tokenizer choice, we introduce n-gram language models as a low-cost proxy and validate their effectiveness by pretraining and finetuning 18 RoBERTa-style encoders for molecular property prediction. To overcome the limitations of existing tokenizers, we propose two new tokenizers -- Smirk and Smirk-GPE -- with full coverage of the OpenSMILES specification. The proposed tokenizers systematically integrate nuclear, electronic, and geometric degrees of freedom; facilitating applications in pharmacology, agriculture, biology, and energy storage. Our results highlight the need for open-vocabulary modeling and chemically diverse benchmarks in cheminformatics.