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Qi Ouyang

Publications and source records attributed to Qi Ouyang.

At least 19 recordsLinked to original sources

When Errors Become Memories: Causal Pathway Tracing in Multi-Turn Memory-Augmented LLMs

Long-term memory enables large language models (LLMs) to preserve and reuse information across interactions, but it can also turn localized errors into persistent risks. Existing work mainly evaluates whether memory systems store and retrieve information correctly, leaving limited understanding of how errors propagate across responses, memory states, and future interactions. We propose a structural causal model (SCM)-based framework for cross-turn error propagation in memory-augmented LLMs. We model user questions, model responses, and memory states as a dynamic causal process, and identify two entry pathways: internal memory updating and external question feedback. By intervening on these pathways, we construct four counterfactual trajectories and quantify their downstream effects and interaction. Error influence is evaluated at four levels: memory retention, natural responses, targeted diagnostic probing, and probability-level error preference. Experiments show that error influence generally decays with interaction distance, while the memory-update pathway contributes more persistent effects than question feedback; latent errors may remain even after disappearing from natural responses. Propagation patterns also vary across memory categories and memory mechanisms. Pathway-guided restoration further validates this decomposition: Question Repair reduces residual error by 27.5%, Memory Repair by 70.2%, and Joint Repair by 98.3%, nearly eliminating residual propagation.

cs.CL

G2VD: Generalizable AI-Generated Video Detection via Counterfactual Intervention and Causal Disentanglement

Rapid advances in AI video generation pose increasing security risks and call for reliable detectors with strong cross-domain generalization. Although existing methods perform well under in-domain evaluation, their performance degrades substantially on unseen generators. A key reason is shortcut learning, where detectors rely on domain-specific bias rather than intrinsic forensic cues. To address this issue, we propose G2VD, a generalizable AI-generated video detection framework based on counterfactual intervention and causal disentanglement. First, G2VD introduces a counterfactual intervention pipeline (CFIPipeline) that constructs counterfactual samples through VAE-based reconstruction and subsequent frequency-domain and pixel-domain alignment, thereby weakening spurious correlations between domain-specific bias and authenticity labels. Building on this intervention, we further design a causal disentanglement classifier that combines two domain-anchored branches with complementary objectives and a constraint based on the Hilbert-Schmidt Independence Criterion (HSIC), encouraging the causal and non-causal representations to capture intrinsic forensic cues and domain-specific bias, respectively. Experiments across four public datasets demonstrate strong cross-domain performance and consistent gains over baseline methods. In the challenging GenVidBench setting, G2VD achieves over 90\% overall ACC, with improvements of 0.194 in F1 and 0.104 in AUC over comparable state-of-the-art methods, while using only 10\% of the available training data. Code is available at https://github.com/DMOSCAR-98/G2VD.

cs.CV

Noise-Driven Exploration and Transient Freezing Select Flat Minima in Stochastic Gradient Descent

Stochastic gradient descent (SGD) is central to deep learning, yet the dynamical origin of its preference for flatter, more generalizable solutions remains unclear. Here, by analyzing SGD learning dynamics, we identify a nonequilibrium mechanism that governs solution selection during training. Numerical experiments reveal a transient exploratory phase in which SGD trajectories repeatedly escape sharp valleys and migrate toward flatter regions of the loss landscape before becoming confined to a final basin. Using a tractable physical model, we show that SGD noise reshapes the loss landscape into an effective potential that preferentially stabilizes flat solutions. We further uncover a transient freezing mechanism: as training progresses, the flattening landscape suppresses transitions between competing valleys. Stronger SGD noise delays this freezing transition, prolonging the exploratory phase and thereby increasing the probability of convergence to flatter minima. Together, these results provide a unified physical framework connecting learning dynamics, loss-landscape geometry, and generalization, and suggest guiding principles for the design of more effective optimization algorithms.

cs.LG

Evolutionary origin of the bipartite architecture of dissipative cellular networks

Recently, plenty research has been done on discovering the role of energy dissipation in biological networks, most of which focus on the relationship of dissipation and functionality. However, the development of networks science urged us to fathom the systematic architecture of biological networks and their evolutionary advantages. We found the dissipation of biological dissipative networks is highly related to their structure. By interrogating these well-adapted networks, we find that the energy producing module is relatively isolated in all situations. We applied evolutionary simulation and analysis on premature networks of classic dissipative networks, namely kinetic proofreading, activator-inhibitor oscillator and two typical adaptative response models. We found despite that selection was imposed merely on the network function, the networks tended to decouple high energy molecules as fuels from the functional module, to achieve higher overall dissipation during the course of evolution. Furthermore, we find that decoupled fuel modules can increase the robustness of the networks towards parameter or structure perturbations. We provide theoretical analysis on the kinetic proofreading networks and the general case of energy-driven networks. We find fuel decoupling can guarantee higher dissipation and, in most cases when considering dissipative networks, higher performance. We conclude that fuel decoupling is an evolutionary outcome and bears benefits during evolution.

physics.bio-ph

Optimal Discretization in Hour-Glass Molecular Clocks Driven by Oscillating Free Energy

Hour-glass clocks do not free-run; they keep time by riding an external rhythm. Motivated by the primordial KaiBC system in cyanobacteria, we study a driven, finite-state molecular clock that advances through a small number of biochemical states under an intrinsic driving energy and a rotating energy landscape set by day-night metabolism. In the continuum limit, coherence is maximized at a resonant operating point where the intrinsic drift matches the driving frequency. In realistic clocks with a finite number of states, discreteness matters: as the rotating landscape sweeps over a lattice of states, it generates a small and high frequency vibration of the collective phase that makes timing inaccurate. Combining the resonant cost with this discreteness penalty yields a trade-off in the number of states: few states are energetically cheap but noisy; many states are precise but costly. The optimum lies at moderate discretization (typically five to fifteen states) and an environmental coupling that is strong enough for responsiveness yet weak enough to avoid large discrete-state vibrations. These design rules rationalize why KaiC's hexameric architecture falls near the predicted optimum and suggest a general principle for hour-glass clocks across organisms.

physics.bio-ph

An altruistic resource-sharing mechanism for synchronization: The energy-speed-accuracy tradeoff

Synchronization among a group of active agents is ubiquitous in nature. Although synchronization based on direct interactions between agents described by the Kuramoto model is well understood, the other general mechanism based on indirect interactions among agents sharing limited resources are less known. Here, we propose a minimal thermodynamically consistent model for the altruistic resource-sharing (ARS) mechanism wherein resources are needed for individual agent to advance but a more advanced agent has a lower competence to obtain resources. We show that while differential competence in ARS mechanism provides a negative feedback leading to synchronization it also breaks detailed balance and thus requires additional energy dissipation besides the cost of driving individual agents. By solving the model analytically, our study reveals a general tradeoff relation between the total energy dissipation rate and the two key performance measures of the system: average speed and synchronization accuracy. For a fixed dissipation rate, there is a distinct speed-accuracy Pareto front traversed by the scarcity of resources: scarcer resources lead to slower speed but more accurate synchronization. Increasing energy dissipation eases this tradeoff by pushing the speed-accuracy Pareto front outwards. The connections of our work to realistic biological systems such as the KaiABC system in cyanobacterial circadian clock and other theoretical results based on thermodynamic uncertainty relation are also discussed.

cond-mat.stat-mech

The Thermodynamic Model to Study the Slow Afterhyperpolarization in a Single Neuron at Different ATP Levels

The neuron consumes energy from ATP hydrolysis to maintain a far-from-equilibrium steady state inside the cell, thus all physiological functions inside the cell are modulated by thermodynamics. The neurons that manage information encoding, transferring, and processing with high energy consumption, displaying a phenomenon called slow afterhyperpolarization after burst firing, whose properties are affected by the energy conditions. Here we constructed a thermodynamical model to quantitatively describe the sAHP process generated by $Na^+-K^+$ ATPases(NKA) and the Calcium-activated potassium(K(Ca)) channels. The model simulates how the amplitude of sAHP is effected by the intracellular ATP concentration and ATP hydrolysis free energy $Δ$ G. The results show a trade-off between NKA and the K(Ca)'s modulation on the sAHP's energy dependence, and also predict an alteration of sAHP's behavior under insufficient ATP supply if the proportion of NKA and K(Ca)'s expression quantities is changed. The research provides insights in understanding the maintenance of neural homeostasis and support furthur researches on metabolism-related and neurodegenerative diseases.

q-bio.NC

Geometry of optimal control in chemical reaction networks

Although optimal control (OC) has been studied in stochastic thermodynamics for systems with continuous state variables, less is known in systems with discrete state variables, such as Chemical Reaction Networks (CRNs). Here, we develop a general theoretical framework to study OC of CRNs for changing the system from an initial distribution of states to a final distribution with minimum dissipation. We derive a ``Kirchhoff's law" for the probability current in the adiabatic limit, from which the optimal kinetic rates are determined analytically for any given probability trajectory. By using the optimal rates, we show that the total dissipation is determined by a $L_2$-distance measure in the probability space and derive an analytical expression for the metric tensor that depends on the probability distribution, network topology, and capacity of each link. Minimizing the total dissipation leads to the geodesic trajectory in the probability space and the corresponding OC protocol is determined by the Kirchhoff's law. To demonstrate our general approach, we use it to find a lower bound for the minimum dissipation that is tighter than existing bounds obtained with only global constraints. We also apply it to simple networks, e.g., fully connected 3-state CRNs with different local constraints and show that indirect pathway and non-functional transient state can play a crucial role in switching between different probability distributions efficiently. Future directions in studying OC in CRNs by using our general framework are discussed.

cond-mat.stat-mech

Nonequilibrium and nonlinear kinetics as key determinants for bistability in fission yeast G2-M transition

A living cell is an open, nonequilibrium biochemical system where ATP hydrolysis serves as the energy source for a wide range of intracellular processes, possibly including the assurance for decision-making. In the fission yeast cell cycle, the transition from G2 to M phase is driven by the activation of Cdc13/Cdc2 and Cdc25 and the deactivation of Wee1 through phosphorylation-dephosphorylation cycles with feedback loops. Here, we present a kinetic description of the G2-M circuit which reveals that both cellular ATP level and ATP hydrolysis free energy critically control Cdc2 activation. Using fission yeast nucleoplasmic extract (YNPE), we experimentally verify that increased ATP level drives the activation of Cdc2 which exhibits bistability and hysteresis in response to changes in cellular ATP level and ATP hydrolysis energy. These findings suggest that cellular ATP level and ATP hydrolysis energy are determinants of the bistability and robustness of Cdc2 activation during G2-M transition.

q-bio.MN

Temperature Compensation through Kinetic Regulation in Biochemical Oscillators

Nearly all circadian clocks maintain a period that is insensitive to temperature changes, a phenomenon known as temperature compensation (TC). Yet, it is unclear whether there is any common feature among different systems that exhibit TC. From a general timescale invariance, we show that TC relies on existence of certain period-lengthening reactions wherein the period of the system increases strongly with the rates in these reactions. By studying several generic oscillator models, we show that this counter-intuitive dependence is nonetheless a common feature of oscillators in the nonlinear (far-from-onset) regime where the oscillation can be separated into fast and slow phases. The increase of the period with the period-lengthening reaction rates occurs when the amplitude of the slow phase in the oscillation increases with these rates while the progression-speed in the slow phase is controlled by other rates of the system. The positive dependence of the period on the period-lengthening rates balances its inverse dependence on other kinetic rates in the system, which gives rise to robust TC in a wide range of parameters. We demonstrate the existence of such period-lengthening reactions and their relevance for TC in all four model systems we considered. Theoretical results for a model of the Kai system are supported by experimental data. A study of the energy dissipation also shows that better TC performance requires higher energy consumption. Our study unveils a general mechanism by which a biochemical oscillator achieves TC by operating at regimes far from the onset where period-lengthening reactions exist.

q-bio.MN

Free energy dissipation enhances spatial accuracy and robustness of Turing pattern in small reaction-diffusion systems

Accurate and robust spatial orders are ubiquitous in living systems. In 1952, Alan Turing proposed an elegant mechanism for pattern formation based on spontaneous breaking of the spatial translational symmetry in the underlying reaction-diffusion system. Much is understood about dynamics and structure of Turing patterns. However, little is known about the energetic cost of Turing pattern. Here, we study nonequilibrium thermodynamics of a small spatially extended biochemical reaction-diffusion system by using analytical and numerical methods. We find that the onset of Turing pattern requires a minimum energy dissipation to drive the nonequilibrium chemical reactions. Above onset, only a small fraction of the total energy expenditure is used to overcome diffusion for maintaining the spatial pattern. We show that the positioning error decreases as energy dissipation increases following the same tradeoff relationship between timing error and energy cost in biochemical oscillatory systems. In a finite system, we find that a specific Turing pattern exists only within a finite range of total molecule number, and energy dissipation broadens the range, which enhances the robustness of the Turing pattern against molecule number fluctuations in living cells. These results are verified in a realistic model of the Muk system underlying DNA segregation in E. coli, and testable predictions are made for the dependence of the accuracy and robustness of the spatial pattern on the ATP/ADP ratio. In general, the theoretical framework developed here can be applied to study nonequilibrium thermodynamics of spatially extended biochemical systems.

cond-mat.stat-mech

Model-based cellular kinetic analysis of SARS-CoV-2 infection: different immune response modes and treatment strategies

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients' data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of naïve T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.

q-bio.PE

Nonequilibrium thermodynamics of coupled molecular oscillators: The energy cost and optimal design for synchronization

A model of coupled molecular oscillators is proposed to study nonequilibrium thermodynamics of synchronization. We find that synchronization of nonequilibrium oscillators costs energy even when the oscillator-oscillator coupling is conservative. By solving the steady state of the many-body system analytically, we show that the system goes through a nonequilibrium phase transition driven by energy dissipation, and the critical energy dissipation depends on both the frequency and strength of the exchange reactions. Moreover, our study reveals the optimal design for achieving maximum synchronization with a fixed energy budget. We apply our general theory to the Kai system in Cyanobacteria circadian clock and predict a relationship between the KaiC ATPase activity and synchronization of the KaiC hexamers. The theoretical framework can be extended to study thermodynamics of collective behaviors in other extended nonequilibrium active systems.

physics.bio-ph

Both cellular ATP level and ATP hydrolysis free energy determine energetically the calcium oscillation in pancreatic $β$-cell

In pancreatic $β$-cells, calcium oscillation signal is the core part of glucose-stimulated insulin secretion. Intracellular calcium concentration oscillates in response to the intake of glucose, which triggers the exocytosis of insulin secretory granules. ATP plays a crucial part in this process. ATP increases as the result of glucose intake, then ATP binds to ATP-sensitive $K^+$ channels ($K_{ATP}$), depolarizes the cell and triggers calcium oscillation, while the ion pumps on the cell membrane consumes the free energy form ATP hydrolysis. Based on Betram et. al. 2004 model, we construct a kinetic models to analyze the thermodynamic characteristics of this system, to reveal how the ATP hydrolysis free energy affects the calcium oscillation. Our results suggest that bifurcation point is sensitive to both the free energy level and cellular ATP level, and the insufficient ATP energy supply would cause dysfunction of calcium oscillation.

q-bio.CB

Critical slowing down and attractive manifold: a mechanism for dynamic robustness in yeast cell-cycle process

The biological processes that execute complex multiple functions, such as cell cycle, must ensure the order of sequential events and keep the dynamic robustness against various fluctuations. Here, we examine the dynamic mechanism and the fundamental structure to achieve these properties in the cell-cycle process of budding yeast Saccharomyces cerevisiae. We show that the budding yeast cell-cycle process behaves like an excitable system containing three well-coupled saddle-node bifurcations to execute DNA replication and mitosis events. The yeast cell-cycle regulatory network can be separated into G1/S phase module, early M module and late M phase module, where the positive feedbacks in each module and the interactions among the modules play important role. If the cell-cycle process operates near the critical points of the saddle-node bifurcations, there is a critical slowing down or ghost effect. This can provide the cell-cycle process with a sufficient duration for each event and an attractive manifold for the state checking of the completion of DNA replication and mitosis; moreover, the fluctuation in the early module/event is forbidden to transmit to the latter module/event. Our results suggest both a fundamental structure of cell-cycle regulatory network and a hint for the evolution of eukaryotic cell-cycle processes, from the dynamic checking mechanism to the molecule checkpoint pathway.

q-bio.MN

The determinant factors for model resolutions obtained using CryoEM method

The CryoEM single particle imaging method has recently received broad attention in the field of structural biology for determining the structures of biological molecules. The structures can be resolved to near-atomic resolutions after rending a large number of CryoEM images measuring molecules in different orientations. However, the factors for model resolution need to be further explored. Here, we provide a theoretical framework in conjunction with numerical simulations to gauge the influence of several key factors that are determinant in model resolution. We found that the number of measured projection images and the quality of each measurement (quantified using average signal-noise-ratio) can be combined to a single factor, which is dominant to the constructed model resolution. Furthermore, the intrinsic thermal motion of the molecules and the defocus levels of the electron microscope both have significant effects on the model resolution. These effects can be quantitatively summarized using an analytical formula that provides a theoretical guideline on structure resolutions for given experimental measurements.

q-bio.BM

A deep convolutional neural network approach to single-particle recognition in cryo-electron microscopy

Background: Single-particle cryo-electron microscopy (cryo-EM) has become a popular tool for structural determination of biological macromolecular complexes. High-resolution cryo-EM reconstruction often requires hundreds of thousands of single-particle images. Particle extraction from experimental micrographs thus can be laborious and presents a major practical bottleneck in cryo-EM structural determination. Existing computational methods of particle picking often use low-resolution templates as inputs for particle matching, making it possible to cause reference-dependent bias. It is critical to develop a highly efficient template-free method to automatically recognize particle images from cryo-EM micrographs. Results: We developed a deep learning-based algorithmic framework, DeepEM, for single-particle recognition from noisy cryo-EM micrographs, enabling automated particle picking, selection and verification in an integrated fashion. The kernel of DeepEM is built upon a convolutional neural network (CNN) of eight layers, which can be recursively trained to be highly "knowledgeable". Our approach exhibits improved performance and high precision when tested on the standard KLH dataset. Application of DeepEM to several challenging experimental cryo-EM datasets demonstrates its capability in avoiding selection of un-wanted particles and non-particles even when true particles contain fewer features. Conclusions: The DeepEM method derived from a deep CNN allows automated particle extraction from raw cryo-EM micrographs in the absence of templates, which demonstrated improved performance, objectivity and accuracy. Application of this novel approach is expected to free the labor involved in single-particle verification, thus promoting the efficiency of cryo-EM data processing.

physics.data-an

Unsupervised single-particle deep clustering via statistical manifold learning

Motivation: Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the assessment of structural heterogeneity. Traditional algorithms for unsupervised classification, such as K-means clustering and maximum likelihood optimization, may classify images into wrong classes with decreasing signal-to-noise-ratio (SNR) in the image data, yet demand increased cost in computation. Overcoming these limitations requires further development on clustering algorithms for high-performance cryo-EM data analysis. Results: Here we introduce a statistical manifold learning algorithm for unsupervised single-particle deep clustering. We show that statistical manifold learning improves classification accuracy by about 40% in the absence of input references for lower SNR data. Applications to several experimental datasets suggest that our deep clustering approach can detect subtle structural difference among classes. Through code optimization over the Intel high-performance computing (HPC) processors, our software implementation can generate thousands of reference-free class averages within several hours from hundreds of thousands of single-particle cryo-EM images, which allows significant improvement in ab initio 3D reconstruction resolution and quality. Our approach has been successfully applied in several structural determination projects. We expect that it provides a powerful computational tool in analyzing highly heterogeneous structural data and assisting in computational purification of single-particle datasets for high-resolution reconstruction.

physics.data-an