Reverse Mode Research Articles

Photoconductivity and bandgap of binary impurity - doped crystalline silicon

The paper presents the results of study of the photoconductivity spectra of sulfur- and <sulfur+manganese>-doped samples of silicon (Si<S>, Si<MnS>) under dark conditions and while samples were subjected to constant light in forward and reverse switching modes. The paper also presents the calculation results of the value of the band gap (Eg ) of <sulfur+zinc> -doped silicon samples (Si<ZnS>). Spatial analogues of generally accepted GaAs structure such as Si2Mn2S and Si2Zn2S are hypothesized to be brought up in the result of above mixed dopings. Tentative investigations of the short-circuit current and open-circuit voltage of p-n-structures, as well as the photoconductivity of such structures, together with the analysis of their lux-ampere characteristic might serve for proposing potential varying band structures for solar cells.

Performance prediction of a centrifugal pump working in direct and reverse mode using Computational Fluid Dynamics

The operation of centrifugal pumps as centripetal turbines can be useful to produce cheap energy in rural zones or developing nations. However, the optimum coupling between the flow and the geometry of the machine cannot be kept in reverse working conditions, and hence the flow instabilities are expected to be much higher. This paper presents a numerical investigation on the unsteady flow in a commercial centrifugal pump operating in direct (pump) and reverse (turbine) mode. Numerical simulations were conducted for several flow rates to investigate the properties of the global flow within the machine. The numerical model was additionally used to estimate the radial load on the impeller, as a function of flow rate, for both modes of operation.

The Standard and Reverse Mode Operation of a Hydrocyclone for Microplastic Separation

Harmonization in the analytical framework is needed to detect, define and further categorize plastics released into the environment. In the range of particles smaller than 200 μm, hydrocyclones (HCs) have proven their capacity in removing microplastics efficiently by offering technical advantages at low operational costs. This publication aims to expand scientific knowledge by introducing four commercially available, low-priced microplastics to a pilot-scale HC setting. The physicochemical characteristics of particles as well as the separation efficiency of the test rig were investigated in depth. Particles with a density of &gt;1000 kg/m3 passed the primary vortex and were discharged into the underflow, allowing us to employ standard mode operation. Particles with a density of &lt;1000 kg/m3 entered the secondary vortex and were removed through the overflow. As expected, separation efficiencies were found to be higher for particles revealing a greater density difference when compared with the mobile phase water. Furthermore, an increase in the inlet volume flow revealed significant positive impacts on the separation efficiency for three plastics to a certain threshold. Data on standard and reverse mode operations presented in this publication can lay out an important source for the harmonization and standardization of future HC research, with the goal of overcoming plastic pollution by developing economically competitive separation processes.

One-dimensional pump geometry prediction modeling for energy loss analysis of pumps working as turbines

Pumps as turbine (PAT) for small-scale hydropower, pressure relief valves, and hydro-pumping applications have recently gained popularity. In contrast to conventional turbines, pumps do not have movable guiding vanes to accommodate changes in flow rate and head. This limits their use to the single best operating point. As a result, the precise estimation of reverse mode operating parameters is critical. One of the most successful techniques in this regard is the energy loss model. However, it necessitates extremely detailed pump geometry and experimental data. Although it is claimed to be more accurate, the lack of data makes it impractical. This calls for the devising of a pump geometrical parameter prediction model from limited manufacturer information. Using 137 sets of commercial pump operating data, geometry redesign was carried out by MATLAB code. Following that, multivariate linear regression analysis was carried out, and a one-dimensional geometrical prediction model was developed. Then the result was validated with computational analysis and measurement. The model results were 99 %, 100 %, and 95 % correlated for pump inlet, volute, and throat inlet diameters, respectively, with the experimental results. Similarly, the model results were also 99 %, 71 %, and 89 % correlated for pump inlet, outlet, and volute blade width, respectively, with experimental results. The model gave a more accurate geometrical result than the analytical and numerical methods.

Differential ray tracing for an efficient computation of the Jacobian in the damped least-squares algorithm

We present a framework for the optimization of optical systems based up on the damped least-squares method and differential ray tracing. First, a mathematical description for the differentiation of the ray-surface intersection is introduced. It is observed that the structure of the optimization variables and operands can be exploited such that the Jacobian for the damped least-squares algorithm can be computed in the same computational complexity as the primal ray tracing for both forward and reverse mode algorithmic differentiation. To demonstrate the advantages of the method a freeform mirror system is analyzed.

Synthesis of Ir Nanoparticles As Promoters for the Stabilization of Fenc-Catalysts Under Ssc Conditions

Fuel cells are promising devices for implementation in automotive propulsion. While the standard operation seems feasible, during start-up and shutdown high potentials occur on the cathodic site induced by the reverse current mode. In consequence, the carbon oxidation reaction (COR) occurs and limits the lifetime of PEMFCs. One approach suppressing carbon corrosion is the introduction of small amounts of an oxygen evolution reaction (OER) catalyst, as e.g. iridium. In our recent work we showed that in relative manner the durability was improved, however, the initial performance was less compared to the non-modified FeNC catalyst.[1 ] These NP had been prepared by a polyol approach.[2 ] However, capping agents (CA) could eventually still be present in these systems, blocking the particles in their performance.Herein, we present our results using an alternative surfactant free synthesis of Ir nanoparticles, adapted from literature,[3 ] that are then used for the modification of an FeNC catalysts. The performance of the newly prepared FeNC+Ir vs the FeNC+Ir+CA reference was evaluated employing accelerated stress tests mimicking the start-up and shut down conditions in RDE and PEMFC. It is shown that with this new approach the amount of NP on the surface can be better controlled. Beside the electrochemical testing structural characterization by X-ray-diffraction, thermogravimetric analysis and transmission-electron-microscopy was performed.It will be shown that by surfactant free synthesis Ir nanoparticles with high purity can be obtained. Due to the higher purity, an improvement of the OER activity can be achieved with the same Ir loading. In the RDE, an improvement in stability was observed by loading an FeNC catalyst with Ir nanoparticles. However, under fuel cell conditions, no improvement in stability was observed by loading Ir nanoparticles onto a FeNC catalyst.List of references[1] Prössl, C., Kübler, M., Paul, S., Ni, L., Kinkelin, S. J., Heppe, N., Eberhardt, K., Geppert, C., Jaegermann, W., Stark, R. W., Bron, M. & Kramm, U. I. (2022). Impact of Ir modification on the durability of FeNC catalysts under start-up and shutdown cycle conditions. Journal of Materials Chemistry A, 10(11), 6038-6053.[2] Prössl, C., Kübler, M., Nowroozi, M. A., Paul, S., Clemens, O., & Kramm, U. I. (2021). Investigation of the thermal removal steps of capping agents in the synthesis of bimetallic iridium-based catalysts for the ethanol oxidation reaction. Physical Chemistry Chemical Physics, 23(1), 563-573.[3] Bizzotto, F., Quinson, J., Schröder, J., Zana, A., & Arenz, M. (2021). Surfactant-free colloidal strategies for highly dispersed and active supported IrO2 catalysts: Synthesis and performance evaluation for the oxygen evolution reaction. Journal of catalysis, 401, 54-62.

Model-Free Bidirectional Synchronous Rectification Control Scheme for LLC-Based Energy Storage System in Electric-Vehicle Energy Router

LLC resonant converters have been widely used in electric-vehicle energy router (EVER) as part of energy storage (ES) system, resulting in the increased demand for bidirectional synchronous rectification (SR) control. However, conventional bidirectional SR schemes are respectively limited by high cost of current sensing, difficulty of high voltage sensing, narrow operating range or high computational burden, especially for EVER. To deal with this problem, this paper proposes a model-free bidirectional SR control scheme for LLC-based ES system in EVER. Firstly, a novel SR tuning principle based on Kirchhoff’s law and phase relationship between inverter control signal and rectifier-side current is proposed. It no longer needs to calculate complicated models. Based on this principle, SR control signals in both forward and reverse modes are tuned by known signals available from main controller in ES system. To this end, no additional sensing component is required and the cost of SR is reduced. Meanwhile, an adaptive DC bus current compensation strategy is designed. It can guarantee high SR accuracy in reverse mode without sensing DC bus current. Moreover, an analog-digital mixed implementation is provided in which signal computation is performed by analog circuit. With these effects, the proposed scheme can achieve bidirectional SR control effectively over a wide operating range with low computational burden on controller. A 400-V/36-V 1-kW bidirectional LLC prototype is built to verify the proposed scheme.

Pumps as turbines for pumped hydro energy storage systems - A small-size case study

Pumped Hydro Energy Storage (PHES) technology has been used since early 1890s and is, nowadays, a consolidated and commercially mature technology. PHES systems allow energy to be stored by pumping water from a lower-to a higher-level reservoir. Subsequently, this energy can be released through a turbine placed in a penstock, which connects the two reservoirs, to produce energy. Although these plants have historically been employed at large power scales (in the order of hundreds of MW), in recent years, micro- and small-scale plants are becoming more interesting, due to their possibility of being integrated with renewable energy systems (RES) used in autonomous island grids. Capital costs associated with hydraulic machines used in PHES systems represent the most critical economic factor, which can be mitigated by using commercial centrifugal pumps in reverse mode (Pumps as Turbines, PATs) in place of small hydro turbines. These expected economic benefits must be weighed in each specific case study, with some drawbacks related to the use of PATs, mainly associated to a lower round-trip efficiency with respect to specifically designed pumps and turbines.In this work, a small-scale PHES plant has been studied coupled to an existent photovoltaic system for the integration in the electric grid of a small island in Southern Italy. Two different PHES outlines have been compared based on techno-economic considerations. The former is a typical PHES system composed of both pumps and a turbine, while the latter uses only an array of parallel pumps which work also in reverse mode. The analysis demonstrates the feasibility of integrating a photovoltaic and PHES plant, which results in a lower cost of electricity production, while PHES performance in the PAT-based outline results penalized by the lower efficiency of PATs with respect to the hydraulic turbine.

On the Flow Physics During the Transition of a Variable Pitch Fan From Nominal Operation to Reverse Thrust Mode

Abstract The flow field during the transition of variable pitch fans (VPFs) from nominal operation to reverse thrust mode at typical “Approach Idle” engine power setting and aircraft touchdown speed of 140 knots is described in this work. An integrated airframe-engine-VPF research model that features a future 40,000 lbf geared high bypass ratio engine installed on a twin-engine airframe in landing configuration is used to explore the flow field in a fully transient unsteady Reynolds-averaged Navier–Stokes (URANS) simulation with imposed wall motion. A novel methodology that implements an adaptation of a mesh displacement equation to mimic the fan blade airfoil rotation is developed. The implementation of this method with gradual, small-step deformation along with an automated mesh update routine enables a high quality, near “real-time” simulation of the complete transition. The flow field during transition is characterized by the evolution from full typical forward flow through the engine to the development of massive recirculation regions at the feather pitch setting and finally to development of a reverse flow from the bypass nozzle to the fan passages. In the paper, the transient development of the various flow features through different stations of the engine flow path apropos the fan blade airfoil rotation to reverse thrust mode are discussed in detail. Also, the temporal development of the mass flow ingested through the engine, airframe decelerating force, and distorted flow at the core engine inlet are described. A hitherto unresolved fan power peaking during the middle of the transition and higher power requirement at reverse thrust mode is captured. The effect of fan rotational speed in terms of engine power setting and the aircraft touchdown velocity on the transition flow physics is explored. A comparison of this fully transient approach with discrete steady-state runs for different stagger angle settings is presented. The flow physics during transition to reverse thrust mode as described in this study is critical in understanding the feasibility of using VPF for reverse thrust in future aircraft. The new capability to study the transition in a fully transient simulation can be used as a design development aid to define design and control characteristics of the reverse thrust VPF.

Synthesis of sodium hypochlorite solutions in coaxial flow cells in current reverse mode

Electrodes made of platinized titanium with a surface platinum content of 2–3 mg/cm2 can be used in non-diaphragm flow- and accumulative-type electrolyzers for the electrolysis of low-concentrated NaCl solutions in order to obtain pure NaClO solutions. If electrolysis of 0.15 M NaCl solution is carried out on platinized titanium electrodes in the usual mode at current densities of 20–40 mA/cm2, then the anode surface passes into an oxidized passive state. In this case, the current efficiency of hypochlorite does not exceed 40%, and the current efficiency of chlorate is more than 20%. During a short electrolysis on a preliminarily reduced surface of platinized titanium, the current efficiency of hypochlorite reaches 90% with almost no accumulation of chlorate. Carrying out the long-term electrolysis of low-concentrated NaCl solutions in the regime of periodic polarity reverse makes it possible to significantly (up to 10 times) reduce the content of chlorate in the resulting sodium hypochlorite solutions. The most promising is the synthesis of sodium hypochlorite solutions in flow-type electrochemical reactors consisting of several series-connected electrochemical modules with an undivided electrode space in the mode of periodic current reverse. The electrolyzer of two series-connected cells in the mode without current reverse allows obtaining a solution that contains 500 mg/L of sodium hypochlorite and 130 mg/L of sodium chlorate. Carrying out the electrolysis in the reverse current mode every 30 s reduces the content of sodium chlorate to 25 mg/L, which makes it possible to produce high-purity NaClO solutions.

Reverse phase, ion exchange, HILIC and mix-mode chromatography for the determination of metformin and evogliptin in human plasma and pharmaceutical formulations

Separation and quantification of highly polar metformin (MTF) alone or in combination with dipeptidyl peptidase-4 inhibitors, such as evogliptin (EVG), sitagliptin, saxagliptin, vildagliptin, linagliptin and teneligliptin, specifically from human plasma and pharmaceutical products is still difficult in mostly preferred ODS based RP-HPLC techniques. Since, owing to weak retention of MTF in ODS, it elutes together with the biological fluid components and drug excipients. Therefore, in this study, alternative to ODS based RP-HPLC, comparatively less known analytical techniques like strong cation exchange chromatography (SCX-3), hydrophilic interaction liquid chromatography (HILIC) and mix-mode chromatography (MMC) were comprehensively evaluated for their potentials and limitations in simultaneous quantification of newly approved EVG and MTF combination (Valera-M). In results, prolonged application of SCX-3, exhibits irreproducible and irreversible retention of MTF and EVG. While in HILIC with Cyano column, excessive acetonitrile as eluent developed the precipitation of MTF and column back pressure. Comparatively, the Acclaimed® mix-mode HILIC-1, demonstrated much promising and reproducible results for MTF and EVG separation and importantly, it can be used either reverse phase or HILIC mode. Considering the overall benefits of Acclaimed® mix-mode HILIC-1, it was used in estimation of MTF and EVG from human plasma and pharmaceutical formulations.

Influence of the platinum surface state on the selectivity of the electrochemical synthesis of sodium hypochlorite

AbstractBACKGROUNDThe synthesis of sodium hypochlorite solutions by electrolysis of low‐concentration and isotonic NaCl solutions using the most available dimensionally stable anodes from platinized titanium is promising from the point of view of the economics of the process. However, such synthesis is seriously complicated by the formation of toxic sodium chlorate impurity.RESULTSIt is shown that in low‐concentration NaCl solutions under anodic polarization, the platinum surface rapidly passes into an oxidized passive state with a NaClO current efficiency (CE) of less than 30% and CE of NaClO3 of more than 20%. Carrying out short‐term electrolysis on the reduced surface of platinum makes it possible to increase the CE of NaClO to almost 90% in the absence of chlorate accumulation. Carrying out electrolysis in the mode of periodic change of electrode polarity (current reverse) allows solving the problem of anode passivation and significantly increasing the purity of the resulting sodium hypochlorite solutions.CONCLUSIONElectrolysis of an isotonic 0.15 mol L−1 NaCl solution in the current reverse mode allows increasing CE(NaClO) from 21% to 40% and significantly decreasing CE(NaClO3) from 21% to 4%. Based on the results obtained, a membraneless electrolyzer can be constructed to produce disinfectant solutions ‘on the spot’ using a commercially available pharmaceutical isotonic solution of NaCl. © 2023 Society of Chemical Industry (SCI).

Modeling Mixtures with PCP-SAFT: Insights from Large-Scale Parametrization and Group-Contribution Method for Binary Interaction Parameters

Vapor/liquid equilibria of mixtures are of utmost importance in the design of chemical processes. Because of the combinatorial complexity of mixtures, the available experimental data are small when considering the large molecular space. To fill this knowledge gap, molecular equations of state like PCP-SAFT show promise due to their explicit consideration of intermolecular interactions that can be transferred to mixtures. In this work, we comprehensively assess and exploit PCP-SAFT for modeling phase equilibria of mixtures. First, we provide binary interaction parameters for 7861 binary systems for which pure-component parameters and experimental data are available. Bubble and dew point pressures are described with a median deviation of 2.3 %. Secondly, we adjust a matrix of binary group/group interaction parameters for the homosegmented and heterosegmented group-contribution (GC) methods for PCP-SAFT. Among 1389 mixtures that can be described with the GC methods, the median deviation in bubble and dew point pressures are 6.4 % for the homosegmented approach and 5.1 % for the heterosegmented approach. The detailed analysis shows the importance of hydrogen bonds in mixtures of non-self-associating components with self-associating components. The parametrization is only possible by introducing a fast numerical method to calculate the derivative of bubble and dew point pressures with respect to arbitrarily many model parameters. The approach leverages reverse mode automatic differentiation (backpropagation), the same method used in machine learning to regress millions of model parameters to large datasets.

Flexible Differentiable Optimization via Model Transformations

We introduce DiffOpt.jl, a Julia library to differentiate through the solution of optimization problems with respect to arbitrary parameters present in the objective and/or constraints. The library builds upon MathOptInterface, thus leveraging the rich ecosystem of solvers and composing well with modeling languages like JuMP. DiffOpt offers both forward and reverse differentiation modes, enabling multiple use cases from hyperparameter optimization to backpropagation and sensitivity analysis, bridging constrained optimization with end-to-end differentiable programming. DiffOpt is built on two known rules for differentiating quadratic programming and conic programming standard forms. However, thanks to its ability to differentiate through model transformations, the user is not limited to these forms and can differentiate with respect to the parameters of any model that can be reformulated into these standard forms. This notably includes programs mixing affine conic constraints and convex quadratic constraints or objective function. History: Accepted by Ted Ralphs, Area Editor for Software Tools. Funding: The work of A. Sharma on DiffOpt.jl was funded by the Google Summer of Code program through NumFocus. M. Besançon was partially supported through the Research Campus Modal funded by the German Federal Ministry of Education and Research [Grant 05M14ZAM, 05M20ZBM]. J. Dias Garcia was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. B. Legat was supported by a BAEF Postdoctoral Fellowship, the NSF [Grant OAC-1835443], and the ERC Adv. [Grant 885682]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0283 ), as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0283 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .

Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy.

A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.

Quantitative determination of cyclic guanosine monoposphate (c-GMP) in rat tissues using liquid chromatography and tandem mass spectrometry

Relevance. Cyclic 3′,5′-guanosine monophosphate is a secondary intracellular messenger that plays a key role in many physiological processes.Quantitative determination of the level of c-GMP in the tissues of laboratory animals is an urgent task of experimental pharmacology and physiology.Purpose of the study. Development of a method for the quantitative determination of cyclic guanosine monophosphate in various tissues of rats using high performance liquid chromatography with mass spectrometric detection.Methods. The biomaterial was homogenized with deionized water. Extraction of c-GMP from homogenates was performed with methanol, acyclovir was used as an internal standard. Detection of c-GMP and acyclovir was performed using a Sciex QTrap 3200MD mass spectrometer, chromatographic separation was performed using an Agilent Technologies 1260 Infinity II HPLC. The mobile phase was methanol and deionized water.Results. Detection of c-GMP was performed by MRM transitions m/z 346.2/152.1; 346.2/135.1, chromatographic determination of c-GMP was performed in reverse phase mode on an Agilent InfinityLab Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm column. The retention time of c-GMP and acyclovir was 7.85 and 7.45 minutes, respectively, the total duration of the chromatographic analysis was 12 minutes. The analytical range of the procedure for determining c-GMP in homogenates was 0.5–1000.0 pmol/ml. The content of c-GMP in the tissues of intact Wistar rats was analyzed using the developed method.Conclusion. The developed bioanalytical HPLC-MS/MS method for the quantitative determination of c-GMP fully complies with the validation requirements. The metrological characteristics of the method make it possible to estimate the content of c-GMP in various tissues of rats with high accuracy.

Investigation of energy loss patterns and pressure fluctuation Spectrum for pump-turbine in the reverse pump mode

Investigation of energy loss patterns and pressure fluctuation Spectrum for pump-turbine in the reverse pump mode

Enhancing Hydropower Generation through Pump as Turbine (PAT) System Optimization

Abstract: Pump as Turbine (PAT) systems, operating in reverse mode to transform mechanical energy into hydraulic energy, pose unique challenges in the pursuit of optimal performance for hydropower generation. This research leverages the power of ANSYS CFD/CFX simulations to delve into the impact of various impeller trimming configurations on the efficiency and effectiveness of PAT systems in the context of hydropower generation. The research involves a systematic approach that includes CAD modeling and meshing to analyze three base models: PAT Case 1 (Ø255 mm, 6 blades), PAT Case 4 (Ø230 mm, 6 blades), and PAT Case 7 (Ø215 mm, 6 blades). To validate the simulations, a comparison is made with reference models (PAT reference Ø255 and 6 blade configuration, PAT reference Ø230 and 6 blade configuration, PAT reference Ø215 and 6 blade configuration). The findings of this study show that increasing the number of blades from 6 to 7 results in significant improvements in head, power output, and efficiency. However, further increases to 8 blades demonstrate diminishing efficiency gains. Moreover, reducing the impeller diameter proves to be a beneficial factor in enhancing overall system performance. Among the configurations tested, the Ø215 mm diameter with 7 blades stands out as the top-performing option. This design offers promising potential for maximizing pump efficiency in practical hydropower applications.

Evaluating subgradients for convex relaxations of dynamic process models by adapting current tools

Global dynamic optimization problems are often represented as nonlinear optimization problems with embedded parametric ordinary differential equations. Deterministic methods for global optimization typically employ subgradients of convex relaxations to construct crucial lower bounds. Our recent work shows that subgradients in dynamic optimization problems may be obtained by adapting standard forward or adjoint sensitivity approaches; the adjoint approach ought to be computationally favorable except for small problems. However, established adjoint implementations are incompatible with established libraries for subgradient evaluation. At FOCAPO/CPC 2023, we outlined an automated proof-of-concept implementation of adjoint subgradient evaluation in C++, adapting the convexification package MC++, the ODE solver CVODES, and our own differentiation and code generation tools. This article details how these tools were nontrivially adapted, to ultimately implement adjoint ODE sensitivities embedded with either the forward or reverse modes of subgradient automatic differentiation (AD). Numerical examples are presented for illustration.

Neuronal and astrocyte NCX isoform/splice variants: How do they participate in Na+ and Ca2+ signalling?

NCX1, NCX2, and NCX3 gene isoforms and their splice variants are characteristically expressed in different regions of the brain. The tissue-specific splice variants of NCX1–3 isoforms show specific expression profiles in neurons and astrocytes, whereas the relevant NCX isoform/splice variants exhibit diverse allosteric modes of Na+- and Ca2+-dependent regulation. In general, overexpression of NCX1–3 genes leads to neuroprotective effects, whereas their ablation gains the opposite results. At this end, the partial contributions of NCX isoform/splice variants to neuroprotective effects remain unresolved. The glutamate-dependent Na+ entry generates Na+ transients (in response to neuronal cell activities), whereas the Na+-driven Ca2+ entry (through the reverse NCX mode) raises Ca2+ transients. This special mode of signal coupling translates Na+ transients into the Ca2+ signals while being a part of synaptic neurotransmission. This mechanism is of general interest since disease-related conditions (ischemia, metabolic stress, and stroke among many others) trigger Na+ and Ca2+ overload with deadly outcomes of downstream apoptosis and excitotoxicity. The recently discovered mechanisms of NCX allosteric regulation indicate that some NCX variants might play a critical role in the dynamic coupling of Na+-driven Ca2+ entry. In contrast, the others are less important or even could be dangerous under altered conditions (e.g., metabolic stress). This working hypothesis can be tested by applying advanced experimental approaches and highly focused computational simulations. This may allow the development of structure-based blockers/activators that can selectively modulate predefined NCX variants to lessen the life-threatening outcomes of excitotoxicity, ischemia, apoptosis, metabolic deprivation, brain injury, and stroke.