Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To perform these often amazing tasks, proteins must move and we must think of them as dynamic ensembles of three dimensional structures formed first by folding the polypeptide chains so as to minimize the conflicts between the interactions of their constituent amino acids. It is apparent however that, even when completely folded, not all conflicting interactions have been resolved so the structure remains "locally frustrated". Over the last decades it has become clearer that this local frustration is not just a random accident but plays an essential part of the inner workings of protein molecules. We will review here the physical origins of the frustration concept and review evidence that local frustration is important for protein physiology, protein-protein recognition, catalysis and allostery. Also, we highlight examples showing how alterations in the local frustration patterns can be linked to distinct pathologies. Finally we explore the extensio
Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a multivolume biochemistry textbook that is part of the LibreText c
The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single body. In contrast, when social interactions occur, molecular and behavioral responses in interacting individuals can lead to physiological processes that are distributed across multiple individuals. In eusocial insect colonies, such multi-body processes are tightly integrated, involving social communication mechanisms that regulate the physiology of colony members. As a result, conserved physiological mechanisms, for example related to pheromone detection and neural signaling pathways, are deployed in novel contexts and regulate emergent colony traits during the evolutionary origin and elaboration of social complexity. Here we review conceptual frameworks for organismal and colony physiology, and highlight functional genomic, physiological, and behavioral research exploring how colony-level traits arise from physical and chemical interactions among nestmates. We highlight mechanistic work exploring how colony traits arise from physical and chemical interactions among physiologically-specialized nestmates of various developmental stages. We consider similari
Speech emotion recognition (SER) is essential for humanoid robot tasks such as social robotic interactions and robotic psychological diagnosis, where interpretable and efficient models are critical for safety and performance. Existing deep models trained on large datasets remain largely uninterpretable, often insufficiently modeling underlying emotional acoustic signals and failing to capture and analyze the core physiology of emotional vocal behaviors. Physiological research on human voices shows that the dynamics of vocal amplitude and phase correlate with emotions through the vocal tract filter and the glottal source. However, most existing deep models solely involve amplitude but fail to couple the physiological features of and between amplitude and phase. Here, we propose PhysioSER, a physiology-informed vocal spectrotemporal representation learning method, to address these issues with a compact, plug-and-play design. PhysioSER constructs amplitude and phase views informed by voice anatomy and physiology (VAP) to complement SSL models for SER. This VAP-informed framework incorporates two parallel workflows: a vocal feature representation branch to decompose vocal signals based
Traditionally, studies in experimental physiology have been conducted in small groups of human participants, animal models or cell lines. Identifying optimal study designs that achieve sufficient power for drawing proper statistical inferences to detect group level effects with small sample sizes has been challenging. Moreover, average effects derived from traditional group-level inference do not necessarily apply to individual participants. Here, we introduce N-of-1 trials as an innovative study design that can be used to draw valid statistical inference about the effects of interventions on individual participants and can be aggregated across multiple study participants to provide population-level inferences more efficiently than standard group randomized trials. N-of-1 trials have been used in healthcare settings since the late 1980s, but without large-scale adoption and with few applications in experimental physiology research settings. In this manuscript, we introduce the key components and design features of N-of-1 trials, describe statistical analysis and interpretations of the results, and describe some available digital tools to facilitate their use using examples from exp
Smart rings offer a convenient way to continuously and unobtrusively monitor cardiovascular physiological signals. However, a gap remains between the ring hardware and reliable methods for estimating cardiovascular parameters, partly due to the lack of publicly available datasets and standardized analysis tools. In this work, we present $τ$-Ring, the first open-source ring-based dataset designed for cardiovascular physiological sensing. The dataset comprises photoplethysmography signals (infrared and red channels) and 3-axis accelerometer data collected from two rings (reflective and transmissive optical paths), with 28.21 hours of raw data from 34 subjects across seven activities. $τ$-Ring encompasses both stationary and motion scenarios, as well as stimulus-evoked abnormal physiological states, annotated with four ground-truth labels: heart rate, respiratory rate, oxygen saturation, and blood pressure. Using our proposed RingTool toolkit, we evaluated three widely-used physics-based methods and four cutting-edge deep learning approaches. Our results show superior performance compared to commercial rings, achieving best MAE values of 5.18 BPM for heart rate, 2.98 BPM for respirato
Study Objectives: Fetal sleep is a vital yet underexplored aspect of prenatal neurodevelopment. Its cyclic organization reflects the maturation of central neural circuits, and disturbances in these patterns may offer some of the earliest detectable signs of neurological compromise. This is the first review to integrate more than seven decades of research into a unified, cross-species synthesis of fetal sleep. We examine: (i) Physiology and Ontogeny-comparing human fetuses with animal models; and (ii) Methodological Evolution-transitioning from invasive neurophysiology to non-invasive monitoring and deep learning frameworks. Methods: A structured narrative synthesis was guided by a systematic literature search across four databases (PubMed, Scopus, IEEE Xplore, and Google Scholar). From 2,925 identified records, 171 studies involving fetal sleep-related physiology, sleep-state classification, or signal-based monitoring were included in this review. Results: Across the 171 studies, fetal sleep states become clearly observable as the brain matures. In fetal sheep and baboons, organized cycling between active and quiet sleep emerges at approximately 80%-90% gestation. In humans, this d
Bacterial physiology is a branch of biology that aims to understand overarching principles of cellular reproduction. Many important issues in bacterial physiology are inherently quantitative, and major contributors to the field have often brought together tools and ways of thinking from multiple disciplines. This article presents a comprehensive overview of major ideas and approaches developed since the early 20th century for anyone who is interested in the fundamental problems in bacterial physiology. This article is divided into two parts. In the first part (Sections 1 to 3), we review the first `golden era' of bacterial physiology from the 1940s to early 1970s and provide a complete list of major references from that period. In the second part (Sections 4 to 7), we explain how the pioneering work from the first golden era has influenced various rediscoveries of general quantitative principles and significant further development in modern bacterial physiology. Specifically, Section 4 presents the history and current progress of the `adder' principle of cell size homeostasis. Section 5 discusses the implications of coarse-graining the cellular protein composition, and how the coar
User performance is crucial in interactive systems, capturing how effectively users engage with task execution. Prospectively predicting performance enables the timely identification of users struggling with task demands. While ocular and cardiac signals are widely used to characterise performance-relevant visual behaviour and physiological activation, their potential for early prediction and for revealing the physiological mechanisms underlying performance differences remains underexplored. We conducted a within-subject experiment in a game environment with naturally unfolding complexity, using early ocular and cardiac signals to predict later performance and to examine physiological and self-reported group differences. Results show that the ocular-cardiac fusion model achieves a balanced accuracy of 0.86, and the ocular-only model shows comparable predictive power. High performers exhibited targeted gaze and adjusted visual sampling, and sustained more stable cardiac activation as demands intensified, with a more positive affective experience. These findings demonstrate the feasibility of cross-session prediction from early physiology, providing interpretable insights into perfor
This paper briefly describes the device - the phytosensor - for measuring physiological and electrophysiological parameters of plants. This system is developed as a bio-physiological sensor in precise agriculture, as a tool in plant research and environmental biology, and for plant enthusiasts in smart home or entertainment applications. The phytosentor measures main physiological parameters such as the leaf transpiration rate, sap flow, tissue conductivity and frequency response, biopotentials (action potentials and variation potentials), and can conduct electrochemical impedance spectroscopy with organic tissues. Soil moisture and temperature, air quality (CO2, NO2, O3 and other sensors on I2C bus), and general environmental parameters (light, temperature, humidity, air pressure, electromagnetic and magnetic fields) are also recorded in real time. In addition to phytosensing, the device can also perform phytoactuation, i.e. execute electrical or light stimulation of plants, control irrigation and lighting modes, conduct fully autonomous experiments with complex feedback-based and adaptive scenarios in robotic or biohybrid systems. This article represents the revised and extended
Foundation models have had a big impact in recent years and billions of dollars are being invested in them in the current AI boom. The more popular ones, such as Chat-GPT, are trained on large amounts of data from the Internet, and then reinforcement learning, RAG, prompt engineering and cognitive modelling are used to fine-tune and augment their behavior. This technology has been used to create models of individual people, such as Caryn Marjorie. However, these chatbots are not based on people's actual emotional and physiological responses to their environment, so they are, at best, surface-level approximations to the characters they are imitating. This paper describes how a new type of foundation model - a first-person foundation model - could be created from recordings of what a person sees and hears as well as their emotional and physiological reactions to these stimuli. A first-person foundation model would map environmental stimuli to a person's emotional and physiological states, and map a person's emotional and physiological states to their behavior. First-person foundation models have many exciting applications, including a new type of recommendation engine, personal assis
Understanding how human health changes over time, and why responses to interventions vary between individuals, remains a central challenge in medicine. Here we present HealthFormer, a decoder-only transformer that models the human physiological trajectory generatively, by training on data from the Human Phenotype Project, a multi-visit cohort of over 15,000 deeply phenotyped individuals. We tokenise each participant's health trajectory across 667 measurements spanning seven domains: blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behaviour and medication exposure. We train HealthFormer to forecast individual physiological trajectories across these domains, and from this single generative objective a range of clinically relevant tasks can be expressed as queries on the model. We show that, without task-specific training, HealthFormer transfers to four independent cohorts and improves prediction for 27 of 30 incident-disease and mortality endpoints, exceeding established clinical risk scores in every comparison. We further show that the model can simulate interventions in silico: in a held-out perso
In anticipation of the completion of the High-Luminosity Large Hadron Collider (HL-LHC) programme by the end of 2041, CERN is preparing to launch a new major facility in the mid-2040s. According to the 2020 update of the European Strategy for Particle Physics (ESPP), the highest-priority next collider is an electron-positron Higgs factory, followed in the longer term by a hadron-hadron collider at the highest achievable energy. The CERN directorate established a Future Colliders Comparative Evaluation working group in June 2023. This group brings together project leaders and domain experts to conduct a consistent evaluation of the Future Circular Collider (FCC) and alternative scenarios based on shared assumptions and standardized criteria. This report presents a comparative evaluation of proposed future collider projects submitted as input for the Update of the European Strategy for Particle Physics. These proposals are compared considering main performance parameters, environmental impact and sustainability, technical maturity, cost of construction and operation, required human resources, and realistic implementation timelines. An overview of the international collider projects w
We aim to characterize the U-band variability of young brown dwarfs in the Taurus Molecular Cloud and discuss its origin. We used the XMM-Newton Extended Survey of the Taurus Molecular Cloud, where a sample of 11 young bona fide brown dwarfs (spectral type later than M6) were observed simultaneously in X-rays with XMM-Newton and in the U-band with the XMM-Newton Optical/UV Monitor (OM). We obtained upper limits to the U-band emission of 10 brown dwarfs (U>19.6-20.6 mag), whereas 2MASSJ04141188+2811535 was detected in the U-band. Remarkably, the magnitude of this brown dwarf increased regularly from U~19.5 mag at the beginning of the observation, peaked 6h later at U~18.4 mag, and then decreased to U~18.65 mag in the next 2h. The first OM U-band measurement is consistent with the quiescent level observed about one year later thanks to ground follow-up observations. This brown dwarf was not detected in X-rays by XMM-Newton during the OM observation. We discuss the possible sources of U-band variability for this young brown dwarf, namely a magnetic flare, non-steady accretion onto the substellar surface, and rotational modulation of a hot spot. We conclude that this event is relate
The increasing use of children's automatic speech recognition (ASR) systems has spurred research efforts to improve the accuracy of models designed for children's speech in recent years. The current approach utilizes either open-source speech foundation models (SFMs) directly or fine-tuning them with children's speech data. These SFMs, whether open-source or fine-tuned for children, often exhibit higher word error rates (WERs) compared to adult speech. However, there is a lack of systemic analysis of the cause of this degraded performance of SFMs. Understanding and addressing the reasons behind this performance disparity is crucial for improving the accuracy of SFMs for children's speech. Our study addresses this gap by investigating the causes of accuracy degradation and the primary contributors to WER in children's speech. In the first part of the study, we conduct a comprehensive benchmarking study on two self-supervised SFMs (Wav2Vec2.0 and Hubert) and two weakly supervised SFMs (Whisper and MMS) across various age groups on two children speech corpora, establishing the raw data for the causal inference analysis in the second part. In the second part of the study, we analyze th
A computational framework integrating optimization algorithms, parallel computing and plant physiology was developed to explore crop ideotype design. The backbone of the framework is a plant physiology model that accurately tracks water use (i.e. a plant hydraulic model) coupled with mass transport (CO2 exchange and transport), energy conversion (leaf temperature due to radiation, convection and mass transfer) and photosynthetic biochemistry of an adult maize plant. For a given trait configuration, soil parameters and hourly weather data, the model computes water use and photosynthetic output over the life of an adult maize plant. We coupled this validated model with a parallel, meta-heuristic optimization algorithm, specifically a genetic algorithm (GA), to identify trait sets (ideotypes) that resulted in desired water use behavior of the adult maize plant. We detail features of the model as well as the implementation details of the coupling with the optimization framework and deployment on high performance computing platforms. We illustrate a representative result of this framework by identifying maize ideotypes with optimized photosynthetic yields using weather and soil conditio
Recent advances in large language models (LLMs) have enabled new possibilities in simulating complex physiological systems. We introduce Organ-Agents, a multi-agent framework that simulates human physiology via LLM-driven agents. Each Simulator models a specific system (e.g., cardiovascular, renal, immune). Training consists of supervised fine-tuning on system-specific time-series data, followed by reinforcement-guided coordination using dynamic reference selection and error correction. We curated data from 7,134 sepsis patients and 7,895 controls, generating high-resolution trajectories across 9 systems and 125 variables. Organ-Agents achieved high simulation accuracy on 4,509 held-out patients, with per-system MSEs <0.16 and robustness across SOFA-based severity strata. External validation on 22,689 ICU patients from two hospitals showed moderate degradation under distribution shifts with stable simulation. Organ-Agents faithfully reproduces critical multi-system events (e.g., hypotension, hyperlactatemia, hypoxemia) with coherent timing and phase progression. Evaluation by 15 critical care physicians confirmed realism and physiological plausibility (mean Likert ratings 3.9 an
This paper describes a general approach to the compartmental modeling of nuclear data based on spectral analysis and statistical optimization. We utilize the renal physiology as test case and validate the method against both synthetic data and real measurements acquired during two micro-PET experiments with murine models.
We present a detailed physiological model of the retina that includes the biochemistry and electrophysiology of phototransduction, neuronal electrical coupling, and the spherical geometry of the eye. The model is a parabolic-elliptic system of partial differential equations based on the mathematical framework of the bi-domain equations, which we have generalized to account for multiple cell-types. We discretize in space with non-uniform finite differences and step through time with a custom adaptive time-stepper that employs a backward differentiation formula and an inexact Newton method. A refinement study confirms the accuracy and efficiency of our numerical method. Numerical simulations using the model compare favorably with experimental findings, such as desensitization to light stimuli and calcium buffering in photoreceptors. Other numerical simulations suggest an interplay between photoreceptor gap junctions and inner segment, but not outer segment, calcium concentration. Applications of this model and simulation include analysis of retinal calcium imaging experiments, the design of electroretinograms, the design of visual prosthetics, and studies of ephaptic coupling within
Understanding and mitigating driving stress is vital for preventing accidents and advancing both road safety and driver well-being. While vehicles are equipped with increasingly sophisticated safety systems, many limits exist in their ability to account for variable driving behaviors and environmental contexts. In this study we examine how short-term stressor events impact drivers' physiology and their behavioral responses behind the wheel. Leveraging a controlled driving simulation setup, we collected physiological signals from 31 adult participants and designed a multimodal machine learning system to estimate the presence of stressors. Our analysis explores the model sensitivity and temporal dynamics against both known and novel emotional inducers, and examines the relationship between predicted stress and observable patterns of vehicle control. Overall, this study demonstrates the potential of linking physiological signals with contextual and behavioral cues in order to improve real-time estimation of driving stress.