Steady-state Conditions Research Articles

Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. The PA vasa vasorum are branches of the BA. The lungs were used either as the control group (n = 3) or the intervention group (n = 8). The protocol for the intervention group was as follows: normoxic ventilation and perfusion (steady state), hypoxic BA perfusion, steady state, and hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady-state conditions for 105 min. During the experiments, PA pressure (PAP) and blood gas analysis were frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible during the second hypoxic BA perfusion. Under control conditions, the PAP stayed constant until about 80 min of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup, suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.NEW & NOTEWORTHY Hypoxic perfusion of the vasa vasorum of the pulmonary artery directly increased pulmonary arterial pressure in an ex vivo lung perfusion setup. This suggests that the function of pulmonary arterial vasa vasorum and wall ischemia may contribute to the development of pulmonary hypertension.

A new method of fuel pebble temperature calculation based on neutronic and thermal coupling equivalent model

As one of the six reactor types in the fourth-generation nuclear energy systems, the Very High Temperature Gas-cooled Reactor (VHTR) possesses inherent safety features. One VHTR fuel pebble contains tens of thousands of randomly distributed TRISO fuel particles, displaying a double heterogeneity characteristic. Current research models employ the homogenized method for fuel pebble temperature calculation, which neglected the neutronic and thermal (N/T) coupling effect and double heterogeneity characteristic. This study proposes a fuel pebble coupled equivalent method (PCEM) for temperature calculation. The method is based on the effective thermal conductivity obtained by the fine structure fuel pebble N/T coupling method. The new method is evaluated on steady-state and transient VHTR multi-scale neutronic and thermal hydraulic (N/TH) coupling calculation. The results show that the traditional temperature calculation method is conservative. Under steady-state conditions, the maximum degree of conservatism of the fuel pebble average temperature and peak temperature are 0.6 K and 14.2 K respectively. For the sudden drop in coolant flow rate transient condition, the average temperature and peak temperature of the fuel pebble calculated by PCEM are smaller than the values calculated by traditional method at the same time. Due to the influence of the fuel Doppler effect, the transient response of the traditional calculation method is slower.

Impact of HO2∕RO2 ratio on highly oxygenated α-pinene photooxidation products and secondary organic aerosol formation potential

Abstract. Highly oxygenated molecules (HOMs) from the atmospheric oxidation of biogenic volatile organic compounds are important contributors to secondary organic aerosol (SOA). Organic peroxy radicals (RO2) and hydroperoxy radicals (HO2) are key species influencing the HOM product distribution. In laboratory studies, experimental requirements often result in overemphasis on RO2 cross-reactions compared to reactions of RO2 with HO2. We analyzed the photochemical formation of HOMs from α-pinene and their potential to contribute to SOA formation under high (≈1/1) and low (≈1/100) HO2/RO2 conditions. As HO2/RO2 > 1 is prevalent in the daytime atmosphere, sufficiently high HO2/RO2 is crucial to mimic atmospheric conditions and to prevent biases by low HO2/RO2 on the HOM product distribution and thus SOA yield. Experiments were performed under steady-state conditions in the new, continuously stirred tank reactor SAPHIR-STAR at Forschungszentrum Jülich. The HO2/RO2 ratio was increased by adding CO while keeping the OH concentration constant. We determined the HOM's SOA formation potential, considering its fraction remaining in the gas phase after seeding with (NH4)2SO4 aerosol. An increase in HO2/RO2 led to a reduction in SOA formation potential, with the main driver being a ∼ 60 % reduction in HOM-accretion products. We also observed a shift in HOM-monomer functionalization from carbonyl to hydroperoxide groups. We determined a reduction of the HOM's SOA formation potential by ∼ 30 % at HO2/RO2 ≈1/1 compared to HO2/RO2 ≈ 1/100. Particle-phase observations measured a similar decrease in SOA mass and yield. Our study shows that too low HO2/RO2 ratios compared to the atmosphere can lead to an overestimation of SOA yields.

Dynamic equilibrium of skeletal muscle macrophage ontogeny in the diaphragm during homeostasis, injury, and recovery

The diaphragm is a unique skeletal muscle due to its continuous activation pattern during the act of breathing. The ontogeny of macrophages, pivotal cells for skeletal muscle maintenance and regeneration, is primarily based on two distinct origins: postnatal bone marrow-derived monocytes and prenatal embryonic progenitors. Here we employed chimeric mice to study the dynamics of these two macrophage populations under different conditions. Traditional chimeric mice generated through whole body irradiation showed virtually complete elimination of the original tissue-resident macrophage pool. We then developed a novel method which employs lead shielding to protect the diaphragm tissue niche from irradiation. This allowed us to determine that up to almost half of tissue-resident macrophages in the diaphragm can be maintained independently from bone marrow-derived monocytes under steady-state conditions. These findings were confirmed by long-term (5 months) parabiosis experiments. Acute diaphragm injury shifted the macrophage balance toward an overwhelming predominance of bone marrow (monocyte)-derived macrophages. However, there was a remarkable reversion to the pre-injury ontological landscape after diaphragm muscle recovery. This diaphragm shielding method permits analysis of the dynamics of macrophage origin and corresponding function under different physiological and pathological conditions. It may be especially useful for studying diseases which are characterized by acute or chronic injury of the diaphragm and accompanying inflammation.

Purity control of simulated moving bed based on advanced fuzzy controller

Simulated moving bed (SMB) technology is considered one of the most successful techniques in chromatographic separation. However, due to the nonlinearity caused by discrete events and sensitivity to numerous separation performance parameters, purity control in SMB systems has been a challenging issue. Fuzzy controllers are increasingly popular in industrial environments due to their simplicity and effectiveness in handling nonlinearity. However, traditional fuzzy controllers used in industry often overlook considerations of error acceleration, resulting in slight deviations from target values under steady-state conditions and oscillatory behavior when system parameters change. This study proposes an advanced fuzzy controller, where in a series of experiments, the purity control targets for component B are set at 94% and 96%, and for component A are set at 96% and 96%, respectively. Experimental results indicate that the advanced fuzzy controller achieves higher precision, with an average deviation of around 0.1%, for both components B and A. Importantly, under variations in adsorbent parameter(from 0.01 to 0.03), feed concentration(from 4.5 to 5.2), and switching time(from 178 to 182), the experimental results demonstrate smoother control with the advanced controller, particularly when oscillations occur with conventional fuzzy controllers due to switching time variations, indicating robust control with the advanced fuzzy controller.

Dual-input configuration of three-phase split-source inverter for photovoltaic systems with independent maximum power point tracking

This paper presents a dual-input configuration for the three-phase split-source inverter (SSI) to be used with photovoltaic (PV) systems, it is denoted as DSSI. Compared to using one SSI for each PV input, the proposed configuration uses a lower number of semiconductors. Thus, lower cost along with higher power density can be acquired. The proposed DSSI inherits the brilliant features of the conventional SSI. This includes continuity of input current and high voltage boosting gain. The proposed DSSI offers independent control for the power extracted from each PV source. Thus, independent maximum power point (MPP) tracking is ensured. In addition, no circulating current between the input ports is generated. Simple modulation technique is developed for the proposed configuration. In addition, the control system design to ensure independent MPP tracking along with power quality requirements is illustrated. Comparative study with other dual-input topologies is presented. Simulation, experimental as well as real-time simulation results for DSSI are presented. The results show good performance under dual- and single-input scenarios. In addition, well dynamic performance is verified. Thus, performance at steady-state and dynamic conditions is validated for the proposed DSSI. An efficiency of 92.3 % is achieved by the experimental prototype.

Simulation and experimental study of the thermal characteristics of a high-speed motorized spindle

Based on the finite element simulation software ANSYS Workbench, this study reports the thermal characteristics of a high-speed motorized spindle. The temperature field distribution and axial thermal deformation of the motorized spindle are then detected on an experimental platform. A comparison between the experimental and simulation results revealed the temperature rise of the motorized spindle during the working process. Under steady-state conditions of the working mo-torized spindle, the temperatures of the front bearing, rear bearing and stator were determined as 20°C, approximately 30°C and 25°C, respectively. The axial thermal elongation of the motorized spindle is approximately 10 μm.

Thermal analysis of 4-phase 8/6 SRM for EV application

This article provides a comprehensive analysis of the thermal characteristics of a 4-phase 8/6 switching reluctance motor (SRM) designed for use in an e-rickshaw (3-wheeler) application. The determination of core and copper losses is achieved through electromagnetic analysis using Finite Element Analysis (FEA). The analysis is conducted via MOTORCAD, a multiphysics design software. This work includes the examination of both static and transient temperature conditions. Static analysis entails the estimation of losses by taking into account the motor's maximum current and operating the motor under steady-state conditions. Transient analysis involves the examination of two separate scenarios. One possesses a simple transient characteristic, while the other possesses a distinct duty cycle. The losses obtained from the electromagnetic analysis are used as the input for the simple transient thermal analysis. During transient analysis involving the duty cycle, losses are assigned to certain operating conditions, such as changes in the operating speed of the motor. This study employs the Lumped Parameter Thermal Network (LPTN), as well as 3D and 2D FEA techniques to conduct thermal analysis. The findings were compared and subsequently given in the article. The findings produced from the LPTN and 3D FEA approaches demonstrate a strong correlation. The motor's maximum temperature is limited to 180 °C. The findings indicate that the highest temperature, both under static and transient conditions, is below the maximum attainable value.

Roadmap for Recommended Guidelines of Leak Detection of Subsea Pipelines

The leak of hydrocarbon-carrying pipelines represents a serious incident, and if it is in a gas line, the economic exposure would be significant due to the high cost of lost or deferred hydrocarbon production. In addition, the leakage of hydrocarbon could pose risks to human life, have an impact on the environment, and could cause an image loss for the operating company. Pipelines are designed to operate at full capacity under steady-state flow conditions. Normal operations may involve day-to-day transients such as the operations of pumps, valves, and changes in production/delivery rates. The basic leak detection problem is to distinguish between the normal operational transients and the occurrence of non-typical process conditions that would indicate a leak. To date, the industry has concentrated on a single-phase flow, primarily of oil, gas, and ethylene. The application of a leak-monitoring system to a particular pipeline system depends on environmental issues, regulatory imperatives, loss prevention of the operating company, and safety policy rather than pipe size and configuration. This paper provides a review of the recommended guidance for leak detection of subsea pipelines in the context of pipeline integrity management. The paper also presents a review of the capability and application of various leak detection techniques that can be used to offer a roadmap to potential users of the leak detection systems.

Characteristics of β-(AlxGa1−x)2O3/Ga2O3 dual-metal gate modulation-doped field-effect transistors simulated by TCAD

β-(AlxGa1−x)2O3/Ga2O3 modulation-doped field-effect transistors (MODFETs) with a dual-metal gate (DMG) architecture are designed, and the electrical characteristics of the DMG device are investigated in comparison with the single-metal gate (SMG) device by the Technology Computer-Aided Design (TCAD) simulation. The results demonstrate that the DMG MODFETs possess a superior transconductance (gm), current gain cut-off frequency (fT), and power gain cut-off frequency (fMAX) than those of SMG transistors, which is attributed to the regulated channel electric field by a DMG structure. With a gate length of 0.1 μm, the peak values of fT/fMAX of the designed DMG MODFET are obtained as 48.6/50.6 GHz, respectively. Moreover, a comprehensive thermal analysis is conducted between the SMG and DMG devices under steady-state and transient conditions. The DMG MODFET exhibits a lower maximum temperature than the SMG counterpart due to the reduced channel electric field, each subjected to the same power dissipation. This finding underscores the potential of the β-(AlxGa1−x)2O3/Ga2O3 MODFET with the DMG architecture as a promising approach for high-power radio frequency operations.

INOS regulates hematopoietic stem and progenitor cells via mitochondrial signaling and is critical for bone marrow regeneration

Hematopoietic stem cells (HSCs) replenish blood cells under steady state and on demand, that exhibit therapeutic potential for Bone marrow failures and leukemia. Redox signaling plays key role in immune cells and hematopoiesis. However, the role of reactive nitrogen species in hematopoiesis remains unclear and requires further investigation. We investigated the significance of inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling in hematopoietic stem and progenitor cells (HSPCs) and hematopoiesis under steady-state and stress conditions. HSCs contain low levels of NO and iNOS under normal conditions, but these increase upon bone marrow stress. iNOS-deficient mice showed subtle changes in peripheral blood cells but significant alterations in HSPCs, including increased HSCs and multipotent progenitors. Surprisingly, iNOS-deficient mice displayed heightened susceptibility and delayed recovery of blood progeny following 5-Fluorouracil (5-FU) induced hematopoietic stress. Loss of quiescence and increased mitochondrial stress, indicated by elevated MitoSOX and MMPhi HSCs, were observed in iNOS-deficient mice. Furthermore, pharmacological approaches to mitigate mitochondrial stress rescued 5-FU-induced HSC death. Conversely, iNOS-NO signaling was required for demand-driven mitochondrial activity and proliferation during hematopoietic recovery, as iNOS-deficient mice and NO signaling inhibitors exhibit reduced mitochondrial activity. In conclusion, our study challenges the conventional view of iNOS-derived NO as a cytotoxic molecule and highlights its intriguing role in HSPCs. Together, our findings provide insights into the crucial role of the iNOS–NO–mitochondrial axis in regulating HSPCs and hematopoiesis.

Product Distribution of Steady-State and Pulsed Electrochemical Regeneration of 1,4-NADH and Integration with Enzymatic Reaction.

The direct electrochemical reduction of nicotinamide adenine dinucleotide (NAD+) results in various products, complicating the regeneration of the crucial 1,4-NADH cofactor for enzymatic reactions. Previous research primarily focused on steady-state polarization to examine potential impacts on product selectivity. However, this study explores the influence of dynamic conditions on the selectivity of NAD+ reduction products by comparing two dynamic profiles with steady-state conditions. Our findings reveal that the main products, including 1,4-NADH, several dimers, and ADP-ribose, remained consistent across all conditions. A minor by-product, 1,6-NADH, was also identified. The product distribution varied depending on the experimental conditions (steady state vs. dynamic) and the concentration of NAD+, with higher concentrations and overpotentials promoting dimerization. The optimal yield of 1,4-NADH was achieved under steady-state conditions with low overpotential and NAD+ concentrations. While dynamic conditions enhanced the 1,4-NADH yield at shorter reaction times, they also resulted in a significant amount of unidentified products. Furthermore, this study assessed the potential of using pulsed electrochemical regeneration of 1,4-NADH with enoate reductase (XenB) for cyclohexenone reduction.

Improving the robustness of distributed secondary control in autonomous microgrids to mitigate the effects of communication delays

Distributed control has been employed in autonomous microgrids (MGs) to attain secondary control goals. However, the reliance of MG’s distributed secondary control on communication makes it vulnerable to degraded performance and the risk of instability due to communication delays. This paper enhances the flexibility of the MG control framework, with each distributed generator incorporating supplementary local feedback signals. This added flexibility strengthens the MG’s ability to counteract disturbances caused by delays and enhances its dynamic performance. The introduction of extra feedback signals has a direct impact on the dynamic response of the MG, leaving its steady-state condition unaffected. In comparison to the methods found in existing literature, the increased flexibility relaxes the inherent trade-off between the objectives of improved transient response and the system’s ability to mitigate disturbances caused by delays. To model the MG, a set of delay differential–algebraic equations (DDAEs) is used. The small-signal linearized model is derived and employed to evaluate the stability of the MG as well as fine-tune the control parameters. The effectiveness of this proposed control structure is demonstrated using the MATLAB/Simulink environment and a controller in the loop (CIL) setup, tested against both fixed universal and asynchronous delays, as well as time-varying delays.

Boosting the efficiency up to 33 % for chalcogenide tin mono-sulfide-based heterojunction solar cell using SCAPS simulation technique

In the present article, an FTO/n-ZnO/SnS/Sb2S3/Au heterojunction photovoltaic cell structure was modeled and the cell performance in terms of output parameters viz. open circuit voltage (Voc), short-circuit current density (Jsc), efficiency (η) and fill factor (FF) by varying carrier concentration, and thickness of different layers involved, was studied at ambient conditions. The overall theoretical performance of the designed photovoltaic cell was examined using SCAPS 1-D simulation programme. The simulation programme operates by resolving semiconductor equations such as the Poisson equation, drift-diffusion equation, and continuity equation for both electrons and holes. The equations are generally solved in one-dimension (1D) in a steady state condition. The role of Sb2S3 HTL on the performance study of tin sulfide chalcogenide-based heterojunction photovoltaic cell (HPVC) was also analyzed. Moreover, the impact of functioning temperature between 273 K and 350 K on the performance of photovoltaic cell was observed, and an increase in temperature resulted in poor performance. The impact of different metal back contact work functions and some more electrical parameters viz. series-shunt resistances, defect concentration of layers and interfaces, and radiative recombination coefficients were also observed on HPVC. The simulation results revealed that the HTL Sb2S3 forms proper band alignment with the SnS chalcogenide absorber layer and enhanced the efficiency, η of HPVC by lessening the carrier recombination at the rear contact side. The dislocation and interface defect reduced significantly which leads to the smooth conduction of hole carriers, therefore, preventing of minority carriers to recombine within the absorber. A significant increase in the efficiency ∼33.24 % together with performance cell parameters Jsc ∼34.38 mA/cm2, Voc ∼1.09 V, and FF ∼88.49 % was observed.

Fluctuation theorem as a special case of Girsanov theorem

Stochastic thermodynamics is an important development in the direction of finding general thermodynamic principles for non-equilibrium systems. We believe stochastic thermodynamics has the potential to benefit from the measure-theoretic framework of stochastic differential equations (SDEs). Toward this, in this work, we show that fluctuation theorem (FT) is a special case of the Girsanov theorem, which is an important result in the theory of SDEs. We report that by employing Girsanov transformation of measures between the forward and the reversed dynamics of a general class of Langevin dynamic systems, we arrive at the integral fluctuation relation. Following the same approach, we derive the FT also for the overdamped case. Our derivation is applicable to both transient and steady state conditions and can also incorporate diffusion coefficients varying as a function of state and time, e.g. in the context of multiplicative noise. We expect that the proposed method will be an easy route towards deriving the FT irrespective of the complexity and non-linearity of the system.

Power Losses Reduction in Three-Phase Unbalanced Distribution Networks Using a Convex Optimization Model in the Complex Domain

This article presents a solution methodology to minimize power losses in three-phase unbalanced distribution networks. This approach involved an efficient complex-domain model that is categorized under mixed-integer convex optimization. The methodology employed consisted of efficient load rotation at each constant power node via a three-phase rotation matrix that allows defining each load connection to minimize the expected power imbalance at the terminals of the substation, as well as the total grid power losses, and improve voltage profile performance at each system phase. The load imbalance, expressed as a percentage, can be defined as a function of the active, reactive, or apparent power. In addition, considering the complex-domain representation of three-phase electrical networks under steady-state conditions, a mixed-integer convex model was formulated to reduce the power imbalances. With the purpose of determining the initial and final power losses of these distribution systems, the successive approximations method was employed to address the three-phase power flow problem. As a result, numerical validations in the IEEE 25-bus system and a 35-node three-phase feeder showed that the final active power losses vary depending on the objective function analyzed. Therefore, for the test feeders studied, it is necessary to evaluate each objective function, with the aim of finding the one that yields the best numerical results. Power losses reductions of about 3.8056 % and 6.8652 % were obtained for both test feeders via the proposed optimization methodology. All numerical validations were performed in the Julia programming environment, using the JuMP optimization tool and the HiGHS solver.

Theoretical analysis of transient counter-flow combustion system fueled by porous biomass particles in a non-premixed configuration under non-adiabatic conditions

The current research aims to implement a reliable analytical model in order to scrutinize the transient behavior of a counter-flow non-premixed combustion system fueled by wet porous biomass particles under non-adiabatic conditions, including several processes such as phase change and dehumidification. A special term is added to the heat equation based on the law of conservation of energy as a means to assess the convective heat loss impacts. In order to analyze the structure of the diffusion flame and predict the time-dependent temperature and mass fractions of reactants distributions, transient forms of energy and mass equations are solved through the asymptotic method. Eventually, the influences of key factors such as equivalence ratio, porosity factor of particles, and reactants Lewis numbers on the flame structure and transient behavior of diffusion flames are elaborately investigated in the non-adiabatic condition, considering convective heat loss and compared to those in the adiabatic condition. The findings reveal that increasing the porosity factor not only improves flame temperature but also leads the flame to be located further from the fuel nozzle. In addition, when the system reaches its steady-state condition, the temperature of the flame formed in the adiabatic condition is about 20 % higher than that formed in the non-adiabatic condition.

A quanta-independent approach for the assessment of strategies to reduce the risk of airborne infection

The Wells-Riley model is extensively used for retrospective and prospective modelling of the risk of airborne transmission of infection in indoor spaces. It is also used when examining the efficacy of various removal and deactivation methods for airborne infectious aerosols in the indoor environment, which is crucial when selecting the most effective infection control technologies. The problem is that the large variation in viral load between individuals makes the Wells-Riley model output very sensitive to the input parameters and may yield a flawed prediction of risk. The absolute infection risk estimated with this model can range from nearly 0 % to 100 % depending on the viral load, even when all other factors, such as removal mechanisms and room geometry, remain unchanged. We therefore propose a novel method that removes this sensitivity to viral load. We define a quanta-independent maximum absolute before-after difference in infection risk that is independent of quanta factors like viral load, physical activity, or the dose-response relationships. The input data needed for a non-steady-state calculation are just the removal rates, room volume, and occupancy duration. Under steady-state conditions the approach provides an elegant solution that is only dependent on removal mechanisms before and after applying infection control measures. We applied this method to compare the impact of relative humidity, ventilation rate and its effectiveness, filtering efficiency, and the use of ultraviolet germicidal irradiation on the infection risk. The results demonstrate that the method provides a comprehensive understanding of the impact of infection control strategies on the risk of airborne infection, enabling rational decisions to be made regarding the most effective strategies in a specific context. The proposed method thus provides a practical tool for mitigation of airborne infection risk.

Thermal and structural analysis of the DONES target system under steady state and transient loading conditions

One of the crucial steps in the European Roadmap to the realisation of fusion energy is the design and construction of the Demo-orientated NEutron Source (DONES) facility. DONES is a fusion-like neutron source, based on the International Fusion Materials Irradiation Facility (IFMIF) concept, aimed at qualifying and testing the materials to be used in fusion reactors. The Target System (TSY) is a crucial system as it is the component where the interactions between deuterons and a liquid lithium target, flowing on a solid surface (i.e. the Back Plate), take place to produce neutrons for irradiating the testing materials. In this regard, an investigation campaign has been performed to evaluate the thermo-mechanical behaviour of the DONES TSY under selected steady state and transient loading conditions, in light of the most recent design updates (new bellows and connection systems). The first part of the assessment concerned the analysis of the TSY under the normal operation steady state loading scenario. A detailed 3D FEM model has been set up, considering the newest updates of the TSY geometry and of the operational parameters, and a thermo-mechanical analysis has been launched. Results have been mainly checked in terms of TSY global deformation, focusing on the Back Plate and on the connecting bellows displacements, in order to exclude overlapping with the High Flux Test Module and misalignments with the beam footprint. Afterwards, since the lithium inlet temperature has been increased from 250 °C to 300 °C, a transient thermo-mechanical analysis of the TSY under the start-up loading conditions has been performed to check if it is able to withstand the hotter lithium flow according to the RCC-MRx criteria. Therefore, the reference pre-heating strategy has been adopted, assessing the thermal and mechanical behaviour of the TSY, focusing on the Back Plate. The obtained results are presented and critically discussed, suggesting important recommendations for the follow-up of the design.

Application of machine learning to predict unbound drug bioavailability in the brain

Purpose: Optimizing brain bioavailability is highly relevant for the development of drugs targeting the central nervous system. Several pharmacokinetic parameters have been used for measuring drug bioavailability in the brain. The most biorelevant among them is possibly the unbound brain-to-plasma partition coefficient, Kpuu,brain,ss, which relates unbound brain and plasma drug concentrations under steady-state conditions. In this study, we developed new in silico models to predict Kpuu,brain,ss.Methods: A manually curated 157-compound dataset was compiled from literature and split into training and test sets using a clustering approach. Additional models were trained with a refined dataset generated by removing known P-gp and/or Breast Cancer Resistance Protein substrates from the original dataset. Different supervised machine learning algorithms have been tested, including Support Vector Machine, Gradient Boosting Machine, k-nearest neighbors, classificatory Partial Least Squares, Random Forest, Extreme Gradient Boosting, Deep Learning and Linear Discriminant Analysis. Good practices of predictive Quantitative Structure-Activity Relationships modeling were followed for the development of the models.Results: The best performance in the complete dataset was achieved by extreme gradient boosting, with an accuracy in the test set of 85.1%. A similar estimation of accuracy was observed in a prospective validation experiment, using a small sample of compounds and comparing predicted unbound brain bioavailability with observed experimental data.Conclusion: New in silico models were developed to predict the Kpuu,brain,ss of drug candidates. The dataset used in this study is publicly disclosed, so that the models may be reproduced, refined, or expanded, as a useful tool to assist drug discovery processes.