Toward Synthetic Physical Fingerprint Targets.

Biometric fingerprint identification hinges on the reliability of its sensors; however, calibrating and standardizing these sensors poses significant challenges, particularly in regards to repeatability and data diversity. To tackle these issues, we propose methodologies for fabricating synthetic 3D fingerprint targets, or phantoms, that closely emulate real human fingerprints. These phantoms enable the precise evaluation and validation of fingerprint sensors under controlled and repeatable conditions. Our research employs laser engraving, 3D printing, and CNC machining techniques, utilizing different materials. We assess the phantoms' fidelity to synthetic fingerprint patterns, intra-class variability, and interoperability across different manufacturing methods. The findings demonstrate that a combination of laser engraving or CNC machining with silicone casting produces finger-like phantoms with high accuracy and consistency for rolled fingerprint recordings. For slap recordings, direct laser engraving of flat silicone targets excels, and in the contactless fingerprint sensor setting, 3D printing and silicone filling provide the most favorable attributes. Our work enables a comprehensive, method-independent comparison of various fabrication methodologies, offering a unique perspective on the strengths and weaknesses of each approach. This facilitates a broader understanding of fingerprint recognition system validation and performance assessment.

Rational Design of Field-Effect Sensors Using Partial Differential Equations, Bayesian Inversion, and Artificial Neural Networks.

Silicon nanowire field-effect transistors are promising devices used to detect minute amounts of different biological species. We introduce the theoretical and computational aspects of forward and backward modeling of biosensitive sensors. Firstly, we introduce a forward system of partial differential equations to model the electrical behavior, and secondly, a backward Bayesian Markov-chain Monte-Carlo method is used to identify the unknown parameters such as the concentration of target molecules. Furthermore, we introduce a machine learning algorithm according to multilayer feed-forward neural networks. The trained model makes it possible to predict the sensor behavior based on the given parameters.

Hyper-Parameter Optimization of Stacked Asymmetric Auto-Encoders for Automatic Personality Traits Perception.

In this work, a method for automatic hyper-parameter tuning of the stacked asymmetric auto-encoder is proposed. In previous work, the deep learning ability to extract personality perception from speech was shown, but hyper-parameter tuning was attained by trial-and-error, which is time-consuming and requires machine learning knowledge. Therefore, obtaining hyper-parameter values is challenging and places limits on deep learning usage. To address this challenge, researchers have applied optimization methods. Although there were successes, the search space is very large due to the large number of deep learning hyper-parameters, which increases the probability of getting stuck in local optima. Researchers have also focused on improving global optimization methods. In this regard, we suggest a novel global optimization method based on the cultural algorithm, multi-island and the concept of parallelism to search this large space smartly. At first, we evaluated our method on three well-known optimization benchmarks and compared the results with recently published papers. Results indicate that the convergence of the proposed method speeds up due to the ability to escape from local optima, and the precision of the results improves dramatically. Afterward, we applied our method to optimize five hyper-parameters of an asymmetric auto-encoder for automatic personality perception. Since inappropriate hyper-parameters lead the network to over-fitting and under-fitting, we used a novel cost function to prevent over-fitting and under-fitting. As observed, the unweighted average recall (accuracy) was improved by 6.52% (9.54%) compared to our previous work and had remarkable outcomes compared to other published personality perception works.

Modeling single-molecule stochastic transport for DNA exo-sequencing in nanopore sensors.

We present a simulation framework for computing the probability that a single molecule reaches the recognition element in a nanopore sensor. The model consists of the Langevin equation for the diffusive motion of small particles driven by external forces and the Poisson-Nernst-Planck-Stokes equations to compute these forces. The model is applied to examine DNA exo-sequencing in α-hemolysin, whose practicability depends on whether isolated DNA monomers reliably migrate into the channel in their correct order. We find that, at moderate voltage, migration fails in the majority of trials if the exonuclease which releases monomers is located farther than 1 nm above the pore entry. However, by tuning the pore to have a higher surface charge, applying a high voltage of 1 V and ensuring the exonuclease stays close to the channel, success rates of over 95% can be achieved.

Brownian-motion based simulation of stochastic reaction-diffusion systems for affinity based sensors.

In this work, we develop a 2D algorithm for stochastic reaction-diffusion systems describing the binding and unbinding of target molecules at the surfaces of affinity-based sensors. In particular, we simulate the detection of DNA oligomers using silicon-nanowire field-effect biosensors. Since these devices are uniform along the nanowire, two dimensions are sufficient to capture the kinetic effects features. The model combines a stochastic ordinary differential equation for the binding and unbinding of target molecules as well as a diffusion equation for their transport in the liquid. A Brownian-motion based algorithm simulates the diffusion process, which is linked to a stochastic-simulation algorithm for association at and dissociation from the surface. The simulation data show that the shape of the cross section of the sensor yields areas with significantly different target-molecule coverage. Different initial conditions are investigated as well in order to aid rational sensor design. A comparison of the association/hybridization behavior for different receptor densities allows optimization of the functionalization setup depending on the target-molecule density.

Fluctuations due to association and dissociation processes at nanowire-biosensor surfaces and their optimal design.

In this work, we calculate the effect of the binding and unbinding of molecules at the surface of a nanowire biosensor on the signal-to-noise ratio of the sensor. We model the fluctuations induced by association and dissociation of target molecules by a stochastic differential equation and extend this approach to a coupled diffusion-reaction system. Where possible, analytic solutions for the signal-to-noise ratio are given. Stochastic simulations are performed wherever closed forms of the solutions cannot be derived. Starting from parameters obtained from experimental data, we simulate DNA hybridization at the sensor surface for different target molecule concentrations in order to optimize the sensor design.

Predictive simulations and optimization of nanowire field-effect PSA sensors including screening.

We apply our self-consistent PDE model for the electrical response of field-effect sensors to the 3D simulation of nanowire PSA (prostate-specific antigen) sensors. The charge concentration in the biofunctionalized boundary layer at the semiconductor-electrolyte interface is calculated using the propka algorithm, and the screening of the biomolecules by the free ions in the liquid is modeled by a sensitivity factor. This comprehensive approach yields excellent agreement with experimental current-voltage characteristics without any fitting parameters. Having verified the numerical model in this manner, we study the sensitivity of nanowire PSA sensors by changing device parameters, making it possible to optimize the devices and revealing the attributes of the optimal field-effect sensor.

Kinetic parameter estimation and fluctuation analysis of CO at SnO2 single nanowires.

In this work, we present calculated numerical values for the kinetic parameters governing adsorption/desorption processes of carbon monoxide at tin dioxide single-nanowire gas sensors. The response of such sensors to pulses of 50 ppm carbon monoxide in nitrogen is investigated at different temperatures to extract the desired information. A rate-equation approach is used to model the reaction kinetics, which results in the problem of determining coefficients in a coupled system of nonlinear ordinary differential equations. The numerical values are computed by inverse-modeling techniques and are then used to simulate the sensor response. With our model, the dynamic response of the sensor due to the gas-surface interaction can be studied in order to find the optimal setup for detection, which is an important step towards selectivity of these devices. We additionally investigate the noise in the current through the nanowire and its changes due to the presence of carbon monoxide in the sensor environment. Here, we propose the use of a wavelet transform to decompose the signal and analyze the noise in the experimental data. This method indicates that some fluctuations are specific for the gas species investigated here.

Development of a Reinforcement Learning Algorithm to Optimize Corticosteroid Therapy in Critically Ill Patients with Sepsis.

BACKGROUND: The optimal indication, dose, and timing of corticosteroids in sepsis is controversial. Here, we used reinforcement learning to derive the optimal steroid policy in septic patients based on data on 3051 ICU admissions from the AmsterdamUMCdb intensive care database. METHODS: We identified septic patients according to the 2016 consensus definition. An actor-critic RL algorithm using ICU mortality as a reward signal was developed to determine the optimal treatment policy from time-series data on 277 clinical parameters. We performed off-policy evaluation and testing in independent subsets to assess the algorithm's performance. RESULTS: Agreement between the RL agent's policy and the actual documented treatment reached 59%. Our RL agent's treatment policy was more restrictive compared to the actual clinician behavior: our algorithm suggested withholding corticosteroids in 62% of the patient states, versus 52% according to the physicians' policy. The 95% lower bound of the expected reward was higher for the RL agent than clinicians' historical decisions. ICU mortality after concordant action in the testing dataset was lower both when corticosteroids had been withheld and when corticosteroids had been prescribed by the virtual agent. The most relevant variables were vital parameters and laboratory values, such as blood pressure, heart rate, leucocyte count, and glycemia. CONCLUSIONS: Individualized use of corticosteroids in sepsis may result in a mortality benefit, but optimal treatment policy may be more restrictive than the routine clinical practice. Whilst external validation is needed, our study motivates a 'precision-medicine' approach to future prospective controlled trials and practice.

Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs.

Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers.

Superhuman performance on sepsis MIMIC-III data by distributional reinforcement learning.

We present a novel setup for treating sepsis using distributional reinforcement learning (RL). Sepsis is a life-threatening medical emergency. Its treatment is considered to be a challenging high-stakes decision-making problem, which has to procedurally account for risk. Treating sepsis by machine learning algorithms is difficult due to a couple of reasons: There is limited and error-afflicted initial data in a highly complex biological system combined with the need to make robust, transparent and safe decisions. We demonstrate a suitable method that combines data imputation by a kNN model using a custom distance with state representation by discretization using clustering, and that enables superhuman decision-making using speedy Q-learning in the framework of distributional RL. Compared to clinicians, the recovery rate is increased by more than 3% on the test data set. Our results illustrate how risk-aware RL agents can play a decisive role in critical situations such as the treatment of sepsis patients, a situation acerbated due to the COVID-19 pandemic (Martineau 2020). In addition, we emphasize the tractability of the methodology and the learning behavior while addressing some criticisms of the previous work (Komorowski et al. 2018) on this topic.

Protein Transport through Nanopores Illuminated by Long-Time-Scale Simulations.

The transport of molecules through nanoscale confined space is relevant in biology, biosensing, and industrial filtration. Microscopically modeling transport through nanopores is required for a fundamental understanding and guiding engineering, but the short duration and low replica number of existing simulation approaches limit statistically relevant insight. Here we explore protein transport in nanopores with a high-throughput computational method that realistically simulates hundreds of up to seconds-long protein trajectories by combining Brownian dynamics and continuum simulation and integrating both driving forces of electroosmosis and electrophoresis. Ionic current traces are computed to enable experimental comparison. By examining three biological and synthetic nanopores, our study answers questions about the kinetics and mechanism of protein transport and additionally reveals insight that is inaccessible from experiments yet relevant for pore design. The discovery of extremely frequent unhindered passage can guide the improvement of biosensor pores to enhance desired biomolecular recognition by pore-tethered receptors. Similarly, experimentally invisible nontarget adsorption to pore walls highlights how to improve recently developed DNA nanopores. Our work can be expanded to pressure-driven flow to model industrial nanofiltration processes.

Uncertainty quantification in epidemiological models for the COVID-19 pandemic.

Mathematical modeling of epidemiological diseases using differential equations are of great importance in order to recognize the characteristics of the diseases and their outbreak. The procedure of modeling consists of two essential components: the first component is to solve the mathematical model numerically, the so-called forward modeling. The second component is to identify the unknown parameter values in the model, which is known as inverse modeling and leads to identifying the epidemiological model more precisely. The main goal of this paper is to develop the forward and inverse modeling of the coronavirus (COVID-19) pandemic using novel computational methodologies in order to accurately estimate and predict the pandemic. This leads to governmental decisions support in implementing effective protective measures and prevention of new outbreaks. To this end, we use the logistic equation and the SIR (susceptible-infected-removed) system of ordinary differential equations to model the spread of the COVID-19 pandemic. For the inverse modeling, we propose Bayesian inversion techniques, which are robust and reliable approaches, in order to estimate the unknown parameters of the epidemiological models. We deploy an adaptive Markov-chain Monte-Carlo (MCMC) algorithm for the estimation of a posteriori probability distribution and confidence intervals for the unknown model parameters as well as for the reproduction number. We perform our analyses on the publicly available data for Austria to estimate the main epidemiological model parameters and to study the effectiveness of the protective measures by the Austrian government. The estimated parameters and the analysis of fatalities provide useful information for decision-makers and makes it possible to perform more realistic forecasts of future outbreaks. According to our Bayesian analysis for the logistic model, the growth rate and the carrying capacity are estimated respectively as 0.28 and 14974. Moreover for the parameters of the SIR model, namely the transmission rate and recovery rate, we estimate 0.36 and 0.06, respectively. Additionally, we obtained an average infectious period of 17 days and a transmission period of 3 days for COVID-19 in Austria. We also estimate the reproduction number over time for Austria. This quantity is estimated around 3 on March 26, when the first recovery was reported. Then it decays to 1 at the beginning of April. Furthermore, we present a fatality analysis for COVID-19 in Austria, which is also of importance for governmental protective decision-making. According to our analysis, the case fatality rate (CFR) is estimated as 4% and a prediction of the number of fatalities for the coming 10 days is also presented. Additionally, the ICU bed usage in Austria indicates that around 2% of the active infected individuals are critical cases and require ICU beds. Therefore, if Austrian governmental protective measures would not have taken place and for instance if the number of active infected cases would have been around five times larger, the ICU bed capacity could have been exceeded.

Bayesian inversion for a biofilm model including quorum sensing.

We propose a mathematical model based on a system of partial differential equations (PDEs) for biofilms. This model describes the time evolution of growth and degradation of biofilms which depend on environmental factors. The proposed model also includes quorum sensing (QS) and describes the cooperation among bacteria when they need to resist against external factors such as antibiotics. The applications include biofilms on teeth and medical implants, in drinking water, cooling water towers, food processing, oil recovery, paper manufacturing, and on ship hulls. We state existence and uniqueness of solutions of the proposed model and implement the mathematical model to discuss numerical simulations of biofilm growth and cooperation. We also determine the unknown parameters of the presented biofilm model by solving the corresponding inverse problem. To this end, we propose Bayesian inversion techniques and the delayed-rejection adaptive-Metropolis (DRAM) algorithm for the simultaneous extraction of multiple parameters from the measurements. These quantities cannot be determined directly from the experiments or from the computational model. Furthermore, we evaluate the presented model by comparing the simulations using the estimated parameter values with the measurement data. The results illustrate a very good agreement between the simulations and the measurements.

A Bayesian estimation method for variational phase-field fracture problems.

In this work, we propose a parameter estimation framework for fracture propagation problems. The fracture problem is described by a phase-field method. Parameter estimation is realized with a Bayesian approach. Here, the focus is on uncertainties arising in the solid material parameters and the critical energy release rate. A reference value (obtained on a sufficiently refined mesh) as the replacement of measurement data will be chosen, and their posterior distribution is obtained. Due to time- and mesh dependencies of the problem, the computational costs can be high. Using Bayesian inversion, we solve the problem on a relatively coarse mesh and fit the parameters. In several numerical examples our proposed framework is substantiated and the obtained load-displacement curves, that are usually the target functions, are matched with the reference values.

A multilevel Monte Carlo finite element method for the stochastic Cahn-Hilliard-Cook equation.

In this paper, we employ the multilevel Monte Carlo finite element method to solve the stochastic Cahn-Hilliard-Cook equation. The Ciarlet-Raviart mixed finite element method is applied to solve the fourth-order equation. In order to estimate the mild solution, we use finite elements for space discretization and the semi-implicit Euler-Maruyama method in time. For the stochastic scheme, we use the multilevel method to decrease the computational cost (compared to the Monte Carlo method). We implement the method to solve three specific numerical examples (both two- and three dimensional) and study the effect of different noise measures.

A new method for selective functionalization of silicon nanowire sensors and Bayesian inversion for its parameters.

In this work, a modification procedure for the functionalization of silicon nanowire (SiNW) is applied in biological field effect transistor (BioFET) system. The proposed method precedes the silanization reaction in a manner that the only SiNW and not its SiO2 substrate is functionalized by (3-Aminopropyl) triethoxysilane (APTES) initiators. This method has an effective role in increasing the sensitivity of BioFET sensors and can be applied in commercial ones. Furthermore, we introduce an efficient computational technique to estimate unknown senor parameters. To that end, Bayesian inversion is used to determine the number of PSA target molecules bound to the receptors in both selective and nonselective SiNWs. The approach is coupled with the Poisson-Boltzmann-drift-diffusion (PBDD) equations to provide a comprehensive system to model all biosensor interactions.

Optimal design of nanowire field-effect troponin sensors.

We propose a design strategy for affinity-based biosensors using nanowires for sensing and measuring biomarker concentration in biological samples. Such sensors have been shown to have superior properties compared to conventional biosensors in terms of LOD (limit of detection), response time, cost, and size. However, there are several parameters affecting the performance of such devices that must be determined. In order to solve the design problem, we have developed a comprehensive model based on stochastic transport equations that makes it possible to optimize the sensing behavior.

Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model.

BACKGROUND AND OBJECTIVES: A knowledge of baseline serum creatinine (bSCr) is mandatory for diagnosing and staging AKI. With often missing values, bSCr is estimated by back-calculation using several equations designed for the estimation of GFR, assuming a "true" GFR of 75 ml/min per 1.73 m(2). Using a data set from a large cardiac surgery cohort, we tested the appropriateness of such an approach and compared estimated and measured bSCr. Moreover, we designed a novel data-driven model (estimated serum creatinine [eSCr]) for estimating bSCr. Finally, we analyzed the extent of AKI and mortality rate misclassifications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data for 8024 patients (2833 women) in our cardiac surgery center were included from 1997 to 2008. Measured and estimated bSCr were plotted against age for men and women. Patients were classified to AKI stages defined by the Kidney Disease Improving Global Outcomes (KDIGO) group. Results were compared with data from another cardiac surgery center in Zurich, Switzerland. RESULTS: The Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration formulae describe higher estimated bSCr values in younger patients, but lower values in older patients compared with the measured bSCr values in both centers. The Pittsburgh Linear Three Variables formula correctly describes the increasing bSCr with age, however, it underestimates the overall bSCr level, being in the range of the 25% quantile of the measured values. Our eSCr model estimated measured bSCr best. AKI stage 1 classification using all formulae, including our eSCr model, was incorrect in 53%-80% of patients in Vienna and in 74%-91% in Zurich; AKI severity (according to KDIGO stages) and also mortality were overestimated. Mortality rate was higher among patients falsely classified into higher KDIGO stages by estimated bSCr. CONCLUSIONS: bSCr values back-estimated using currently available eGFR formulae are inaccurate and cannot correctly classify AKI stages. Our model eSCr improves the prediction of AKI but to a still inadequate extent.

Determination of surface concentrations of individual molecule-layers used in nanoscale biosensors by in situ ATR-FTIR spectroscopy.

For the development of nanowire sensors for chemical and medical detection purposes, the optimal functionalization of the surface is a mandatory component. Quantitative ATR-FTIR spectroscopy was used in situ to investigate the step-by-step layer formation of typical functionalization protocols and to determine the respective molecule surface concentrations. BSA, anti-TNF-α and anti-PSA antibodies were bound via 3-(trimethoxy)butylsilyl aldehyde linkers to silicon-oxide surfaces in order to investigate surface functionalization of nanowires. Maximum determined surface concentrations were 7.17 × 10(-13) mol cm(-2) for BSA, 1.7 × 10(-13) mol cm(-2) for anti-TNF-α antibody, 6.1 × 10(-13) mol cm(-2) for anti-PSA antibody, 3.88 × 10(-13) mol cm(-2) for TNF-α and 7.0 × 10(-13) mol cm(-2) for PSA. Furthermore we performed antibody-antigen binding experiments and determined the specific binding ratios. The maximum possible ratio of 2 was obtained at bulk concentrations of the antigen in the µg ml(-1) range for TNF-α and PSA.