Quantitative Biology

Microbial fuel cells implemented in constructed wetlands (CW-MFCs), albeit a relatively new technology still under study, have shown to improve treatment efficiency of urban wastewater. So far the vast majority of CW-MFC systems investigated were designed as lab-scale systems working under rather unrealistic hydraulic conditions using synthetic wastewater. The main objective of this work was to quantify CW-MFCs performance operated under different conditions in a more realistic setup using meso-scale systems with horizontal flow fed with real urban wastewater. Operational conditions tested were organic loading rate (4.9+-1.6, 6.7+-1.4 and 13.6+-3.2 g COD/m2.day) and hydraulic regime (continuous vs intermittent feeding) as well as different electrical connections: CW control (conventional CW without electrodes), open-circuit CW-MFC (external circuit between anode and cathode not connected) and closed-circuit CW-MFC (external circuit connected). Eight horizontal subsurface flow CWs were operated for about four months. Each wetland consisted of a PVC reservoir of 0.193 m2 filled with 4/8 mm granitic riverine gravel. All wetlands had intermediate sampling points for gravel and interstitial liquid sampling. The CW-MFCs were designed as three MFCs incorporated one after the other along the flow path of the CWs. Results showed no significant differences between tested organic loading rates, hydraulic regimes or electrical connections, however, on average, systems operated in closed-circuit CW-MFC mode under continuous flow outperformed the other experimental conditions. Closed-circuit CW-MFC compared to conventional CW control systems showed around 5% and 22% higher COD and ammonium removal, respectively. Correspondingly, overall bacteria activity, as measured by the fluorescein diacetate technique, was higher (4% to 34%) in closed-circuit systems when compared to CW control systems.

Time-resolved analysis of periodically excited luminescence decays by the phasor method in the presence of time-gating or binning is revisited. Analytical expressions for discrete configurations of square gates are derived and the locus of the phasors of such modified periodic single-exponential decays is compared to the canonical uni-versal semicircle. The effects of IRF offset, decay truncation and gate shape are also discussed. Finally, modified expressions for the phase and modulus lifetimes are pro-vided for some simple cases. A discussion of a modified phasor calibration approach is presented, and illustration of the new concepts with examples from the literature conclude this work.

Network control theory has recently emerged as a promising approach for understanding brain function and dynamics. By operationalizing notions of control theory for brain networks, it offers a fundamental explanation for how brain dynamics may be regulated by structural connectivity. While powerful, the approach does not currently consider other non-structural explanations of brain dynamics. Here we extend the analysis of network controllability by formalizing the evolution of neural signals as a function of effective inter-regional coupling and pairwise signal covariance. We find that functional controllability characterizes a region's impact on the capacity for the whole system to shift between states, and significantly predicts individual difference in performance on cognitively demanding tasks including those task working memory, language, and emotional intelligence. When comparing measurements from functional and structural controllability, we observed consistent relations between average and modal controllability, supporting prior work. In the same comparison, we also observed distinct relations between controllability and synchronizability, reflecting the additional information obtained from functional signals. Our work suggests that network control theory can serve as a systematic analysis tool to understand the energetics of brain state transitions, associated cognitive processes, and subsequent behaviors.

OpenSim is a widely used biomechanics simulator with several anatomically accurate human musculo-skeletal models. While OpenSim provides useful tools to analyse human movement, it is not fast enough to be routinely used for emerging research directions, e.g., learning and simulating motor control through deep neural networks and Reinforcement Learning (RL). We propose a framework for converting OpenSim models to MuJoCo, the de facto simulator in machine learning research, which itself lacks accurate musculo-skeletal human models. We show that with a few simple approximations of anatomical details, an OpenSim model can be automatically converted to a MuJoCo version that runs up to 600 times faster. We also demonstrate an approach to computationally optimize MuJoCo model parameters so that forward simulations of both simulators produce similar results.

The deluge of single-cell data obtained by sequencing, imaging and epigenetic markers has led to an increasingly detailed description of cell state. However, it remains challenging to identify how cells transition between different states, in part because data are typically limited to snapshots in time. A prerequisite for inferring cell state transitions from such snapshots is to distinguish whether transitions are coupled to cell divisions. To address this, we present two minimal branching process models of cell division and differentiation in a well-mixed population. These models describe dynamics where differentiation and division are coupled or uncoupled. For each model, we derive analytic expressions for each subpopulation's mean and variance and for the likelihood, allowing exact Bayesian parameter inference and model selection in the idealised case of fully observed trajectories of differentiation and division events. In the case of snapshots, we present a sample path algorithm and use this to predict optimal temporal spacing of measurements for experimental design. We then apply this methodology to an \textit{in vitro} dataset assaying the clonal growth of epiblast stem cells in culture conditions promoting self-renewal or differentiation. Here, the larger number of cell states necessitates approximate Bayesian computation. For both culture conditions, our inference supports the model where cell state transitions are coupled to division. For culture conditions promoting differentiation, our analysis indicates a possible shift in dynamics, with these processes becoming more coupled over time.

This study investigates whether coupling crop modeling and machine learning (ML) improves corn yield predictions in the US Corn Belt. The main objectives are to explore whether a hybrid approach (crop modeling + ML) would result in better predictions, investigate which combinations of hybrid models provide the most accurate predictions, and determine the features from the crop modeling that are most effective to be integrated with ML for corn yield prediction. Five ML models (linear regression, LASSO, LightGBM, random forest, and XGBoost) and six ensemble models have been designed to address the research question. The results suggest that adding simulation crop model variables (APSIM) as input features to ML models can decrease yield prediction root mean squared error (RMSE) from 7 to 20%. Furthermore, we investigated partial inclusion of APSIM features in the ML prediction models and we found soil moisture related APSIM variables are most influential on the ML predictions followed by crop-related and phenology-related variables. Finally, based on feature importance measure, it has been observed that simulated APSIM average drought stress and average water table depth during the growing season are the most important APSIM inputs to ML. This result indicates that weather information alone is not sufficient and ML models need more hydrological inputs to make improved yield predictions.

Open biochemical systems of interacting molecules are ubiquitous in life-related processes. However, established computational methodologies, like molecular dynamics, are still mostly constrained to closed systems and timescales too small to be relevant for life processes. Alternatively, particle-based reaction-diffusion models are currently the most accurate and computationally feasible approach at these scales. Their efficiency lies in modeling entire molecules as particles that can diffuse and interact with each other. In this work, we develop modeling and numerical schemes for particle-based reaction-diffusion in an open setting, where the reservoirs are mediated by reaction-diffusion PDEs. We derive two important theoretical results. The first one is the mean-field for open systems of diffusing particles; the second one is the mean-field for a particle-based reaction-diffusion system with second-order reactions. We employ these two results to develop a numerical scheme that consistently couples particle-based reaction-diffusion processes with reaction-diffusion PDEs. This allows modeling open biochemical systems in contact with reservoirs that are time-dependent and spatially inhomogeneous, as in many relevant real-world applications.

Cox-nnet is a neural-network based prognosis prediction method, originally applied to genomics data. Here we propose the version 2 of Cox-nnet, with significant improvement on efficiency and interpretability, making it suitable to predict prognosis based on large-scale electronic medical records (EMR) datasets. We also add permutation-based feature importance scores and the direction of feature coefficients. Applying on an EMR dataset of OPTN kidney transplantation, Cox-nnet v2.0 reduces the training time of Cox-nnet up to 32 folds (n=10,000) and achieves better prediction accuracy than Cox-PH (p<0.05). Availability and implementation: Cox-nnet v2.0 is freely available to the public at this https URL

In this paper, we examine cross-country differences, in terms of the age distribution of symptomatic cases, hospitalizations, intensive care unit (ICU) cases, and fatalities due to the novel COVID-19. By calculating conditional probabilities, we bridge country-level incidence data gathered from different countries and attribute the variability in data to country demographics. We then provide case, hospitalization, ICU, and fatality estimates for a comprehensive list of countries using the existing data from a variety of countries.

Thanks to automated cryo-EM and GPU-accelerated processing, single-particle cryo-EM has become a rapid structure determination method that permits capture of dynamical structures of molecules in solution, which has been recently demonstrated by the determination of COVID-19 spike protein in March, shortly after its breakout in late January 2020. This rapidity is critical for vaccine development in response to emerging pandemic. This explains why a 2D classification approach based on multi-reference alignment (MRA) is not as popular as the Bayesian-based approach despite that the former has advantage in differentiating structural variations under low signal-to-noise ratio. This is perhaps because that MRA is a time-consuming process and a modular GPU-acceleration library for MRA is lacking. Here, we introduce a library called Cryo-RALib that expands the functionality of CUDA library used by GPU ISAC. It contains a GPU-accelerated MRA routine for accelerating MRA-based classification algorithms. In addition, we connect the cryo-EM image analysis with the python data science stack so as to make it easier for users to perform data analysis and visualization. Benchmarking on the TaiWan Computing Cloud (TWCC) container shows that our implementation can accelerate the computation by one order of magnitude. The library is available at this https URL.