Jülich Aachen Research Alliance

• Extend optimal experimental design for guaranteed parameter estimation to LLE systems • Employ rigorous calculations for the LLE using the Baker’s criterion • Avoid problematic parameter values, which may lead to erroneous predictions • Present proof-of-concept case study, reducing the parameter uncertainty by at least 10.3924909 % Semi-empirical models for LLE are essential for chemical process design but rely on experimental data for parameter estimation. In the face of high experimental costs, determining an informative experimental plan is crucial for constructing and validating these models efficiently. OED for (bounded-error) guaranteed GPE is a valuable approach to planning LLE experiments, but it has been limited to systems with simple input-output relations. We extend this method to systems whose input-output relation is implicitly given by an equation system with additional semi-infinite constraints, which corresponds to the rigorous computation of an LLE. Excess Gibbs free energy models are highly flexible but can predict spurious phase splits due to (i) using non-rigorous computations, or (ii) parameter values that are problematic in the sense that they lead to erroneous model behavior. To mitigate these issues in experiment planning, we (i) employ rigorous calculations using Baker’s criterion, and (ii) enforce additional requirements, based on [Mitsos et al. Chem. Eng. Sci., 64(3):548–559, 2009] to exclude parameter values that lead to erroneous model behavior. We solve the resulting problem using (generalized) semi-infinite programming techniques and provide a proof of concept using the Redlich-Kister model to plan the OED to reduce parameter uncertainty. Our approach successfully avoids wrong predictions due to problematic parameter values and computes an experimental design that significantly reduces the predicted parameter uncertainty. However, our method is computationally demanding, necessitating advancements in numerical methods for practical applications involving multiple parameters or more complex excess models.

Bio-based carboxylic acids are key platform chemicals for a circular economy, offering sustainable alternatives to fossil-derived products. Yet, high substrate and processing costs, along with narrow profit margins, restrict industrial-scale bioproduction. In situ product removal (ISPR) holds the potential to increase productivity and yield in fermentations by circumventing product inhibition. Thus, it presents a promising process intensification measure to bridge the commercial gap between bio-based and petrochemical platform chemicals. One effective method for product recovery is reactive extraction with trioctylamine. In the present study, this method was applied to itaconic acid (ITA) fermentations with Ustilago cynodontis. First, the successful operation of dispersion-based apparatuses for reactive extraction was proven using small-scale mixer-settlers, with 1-octanol and the biocompatible 2-octanone as diluents. We then developed an improved feeding profile, lowering byproduct formation by 72%. Subsequently, we demonstrated the feasibility of ISPR using a perfusion bioreactor with an external membrane coupled to reactive extraction and back-extraction. After 233h of fermentation, the total amount of ITA produced was increased by 26%, and productivity was 21% higher compared to extended-batch fermentations. However, the yield was only slightly improved by 5%. Ultimately, we identified product toxicity far below the maximum titer of 80g as a key bottleneck in ISPR fermentations with U.cynodontis. The results underscore the potential of ISPR and warrant further investigation in this field.

Abstract The transformation of sensory information into goal-directed motor plans and actions is known to emerge from coordinated activity between parietal and motor areas. Within this network, anticipation plays a critical role, enabling the brain to predict upcoming sensory inputs and prepare appropriate actions before sensory information becomes available. However, it remains unclear whether fronto-parietal interactions during motor anticipation follow a serial hierarchical organization or reflect distributed and reciprocal processing. To address this open question, we trained two rhesus macaques to perform a visually-guided sequential reaching task, in which the predictability of target location increased within the sequence. Analysis of eye and hand movements revealed that the degree of movement anticipation increased with target predictability. The direction of the upcoming reach toward predictable targets could be decoded from preparatory neural activity prior to target onset in both dorsal premotor-primary motor cortex (PMd/M1) and parietal area 7A. Using feature-specific information transfer analysis, we found that information about the upcoming movement direction was transmitted between 7A and PMd/M1 through bidirectional, yet asymmetric, interactions. Contrary to classical hierarchical models predicting serial activation across parietal and motor areas, parietal-to-motor interactions did not occur earlier than motor-to-parietal interactions. Instead, our findings support a heterarchical and reciprocal fronto-parietal network in which anticipatory processes adjust the timing of preparatory activity to facilitate eye-hand coordination during reaches to predictable targets.

Epitaxial heterostructures of iron oxide thin films on oxide substrates are promising for spintronic applications. Scaling down such heterostructures into ordered nanostructures enables integration into functional devices. However, fabricating well-ordered nanostructures while retaining their structural and functional integrity remains challenging. A bottom-up approach is used to grow epitaxial Fe3O4 nanodot arrays on Nb-doped SrTiO3(Nb:STO) substrates integrating anodic aluminum oxide (AAO) templates combined with pulsed laser deposition. Following this method, the lateral confinement of Fe3O4 into 30 and 70nm nanodots with 3D long-range ordering is then confirmed by grazing-incidence small-angle X-ray scattering (GISAXS) and scanning electron microscopy (SEM). Building on this structural evidence, the Verwey transition is found to be retained, as observed in the continuous film. To explore its applicability in nanoelectronics, conductive atomic force microscopy (c-AFM) is used to probe local electrical behavior, and reveals bipolar resistive switching at room temperature in individual nanodots, consistent with behavior observed in thin films. Together, these results establish the first demonstration of ordered epitaxial Fe3O4/Nb:STO nanodots with preserved structural, magnetic, and electrical functionalities, providing a generalizable route for nanoscale integration of complexoxides.

Working memory (WM) deficits are common in psychiatric disorders that are associated with decreased prefrontal cortex activity. As WM is essential for cognitive functions, deficits interfere with daily life and treatment. The lateralization of WM components remains unclear, but stimuli matching, often assessed using the n-back task, has been associated with right-hemispheric dominance. This study examines whether anodal transcranial direct current stimulation (tDCS) targeting the right dorsolateral prefrontal cortex (DLPFC) could enhance WM performance in alcohol-dependent patients (AD), tobacco users (TU) and healthy controls (HC). In a double-blind, sham-controlled study, tDCS was applied to upregulate right DLPFC activity. A total of 46 participants received anodal tDCS with a current intensity of 1.5 mA for 20 min or sham stimulation. In addition to the 7x5cm anode, a large reference electrode (10x10cm) was situated over the contralateral supraorbital area. While being stimulated, participants performed the n-back task as a measure of WM performance. Results revealed no significant differences in WM performance between active and sham stimulated participants, nor between groups, and no significant interaction between stimulation condition and group. Bayesian analysis supported the null effects. These findings do not provide evidence that single-session right DLPFC stimulation reliably enhances working memory across all stimulus types. The outcomes may have been influenced by task–stimulation mismatch, sample heterogeneity, small sample size, and stimulation parameters, which could limit the ability to detect subtle tDCS effects in both clinical and healthy populations.

When developing a biotechnological process, the microorganism is first designed, e.g., using metabolic engineering. Then, the optimum fermentation parameters are determined on a laboratory scale, and lastly, they are transferred to the bioreactor scale. However, this step-by-step approach is costly and time-consuming and may result in suboptimal configurations. Herein, we present the bilevel optimization formulation SimulKnockReactor , which connects bioreactor design with microbial strain design, an extension of our previous formulation, SimulKnock (Ziegler et al., 2024). At the upper (bioreactor) level, we minimize investment and operation costs for agitation, aeration, and pH control by determining the size and operating conditions of a continuous stirred-tank reactor—without selecting specific devices like the stirrer type. The lower (cellular) level is based on flux balance analysis and implements optimal reaction knockouts predicted by the upper level. Our results with a core and a genome-scale metabolic model of Escherichia coli show that the substrate is the largest cost factor. Our simultaneous approach outperforms a sequential approach using OptKnock. Namely, the knockouts proposed by OptKnock cannot guarantee the required production capacity in all cases considered. SimulKnockReactor, on the other hand, provides solutions in all cases considered, highlighting the advantage of combining cellular and bioreactor levels. This work is a further step towards a fully integrated bioprocess design. • SimulKnockReactor connects the micro-level with the macro-level of a bioprocess. • SimulKnockReactor proposes optimal gene deletions and minimized bioreactor costs. • CAPEX and OPEX are considered for reactor, oxygen supply, pH control, and cooling. • SimulKnockReactor finds feasible solutions in more cases than a sequential design approach. • The implementation of SimulKnockReactor is openly available.

Chemical membrane degradation has a significant impact on the lifetime of PEM electrolyzers. For a comprehensive understanding of chemical membrane degradation, cell-level models are useful. However, existing cell-level models ignore the dynamic degradation process of PFSA membranes and do not consider the influence of operating parameters, such as pressure. To address these limitations, we present a dynamic cell-level model in which chemical membrane degradation is represented by the fluoride release rate (FRR). The model is lumped (0D in space), and parameters are estimated with literature data using a pseudo–steady-state approach. The model is then applied to investigate the influence of pressure. The results show increased FRR and H2O2 concentrations at higher pressures due to enhanced O2 crossover. A maximum in the degradation rate arises at intermediate current densities due to the interplay of electro-osmotic drag and back-diffusion, which maximizes in-membrane radical (•OH) concentrations, while at higher current densities washout and Fe2+ limitation reduce them. Time-dependent simulations with full dynamics further indicate that the maximum is reached only after several thousand hours.

Abstract This perspective explores how film thickness influences the optical and vibrational properties of crystalline chalcogenide and pnictogen thin films. Measurements of the dielectric function reveal systematic property trends within these families of materials. A distinct class, including crystalline bismuth (Bi), germanium telluride (GeTe), and antimony telluride (Sb 2 Te 3 ), exhibits strong responses to electromagnetic wave excitation. These materials are characterized by large values of the optical dielectric constant ɛ ∞ and high maximum values of ɛ 2 (ω). Crystalline GeTe, Bi and Sb 2 Te 3 furthermore display an unconventional bond rupture observed via atom probe tomography. They utilize a bonding mechanism (metavalent bonding) that balances electron localization typical in iono‐covalent solids with electron delocalization found in metals. In contrast, crystalline Sb 2 Se 3 , In 2 Te 3 , and amorphous GeTe neither exhibit these distinctive characteristics nor the bond rupture pattern. Significant changes in optical and vibrational properties occur with varying film thicknesses for the metavalent solids, i.e., crystalline Bi, GeTe, and Sb 2 Te 3 . For instance, substantial shifts in phonon frequencies are observed in these solids as thickness decreases, reaching frequency shifts up to 30%. This unusual dependence contrasts with covalent counterparts (In 2 Te 3 , amorphous GeTe), which show minimal effects. These findings underscore the potential of metavalent bonding for tailoring materials in optoelectronic applications.