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Domain walls are quasi-one-dimensional topological defects in ferroic materials, which can harbor emergent functionalities. In the case of ferroelectric domain wall (FEDW) devices, an exciting frontier has emerged: memristor-based information storage and processing approaches. Memristor solid-state FEDW devices presented thus far, however predominantly utilize a complex network of domain walls to achieve the desired regulation of density and charge state. Here, using epitaxial bismuth ferrite thin films as a prototype ferroelectric and advanced scanning probe microscopy and stroboscopic methods, we demonstrate controlled single-wall memristive behavior through deterministic electric field-driven conformal changes. Our design exploits memristive functionality through surface pinning of topological domain walls. That is, although the FEDW is constricted by the surface, it is free to twist in the thickness direction. The resulting vertical variation of FEDW morphology creates a complex interplay between surface-induced pinning and field-induced wall bending. This gives rise to metastable electronic transitions, and hence memristive attributes. Moreover, being a single FEDW memristor, once injected there is no need for repeated injection or erasure. Microscopic insight into device operation from phase field modeling indicates controllable warping of the wall, causing memristive conductivity changes. Our results reaffirm the promise of FEDWS for brain-inspired neuromorphic and in-memory computing applications based on integrated ferroelectric devices.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 107cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients (n= 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038.

ABSTRACTStudents’ learning environments often change during school career, due to school transitions and the introduction of educational innovations, causing discontinuity in teaching and learning. Success of students entering a new learning environment depends in part on their prior expectations of education, as these influence later perceptions. Heterogeneity between students, however, needs to be acknowledged. In seeking to determine expectation profiles and their potential linkage to divergent perceptions of education, we longitudinally surveyed secondary school students regarding their expectations before, and their perceptions one and two years after entering an innovative learning environment. We identified three expectation profiles that differed in terms of students’ motivation, learning conceptions, and affective strategies: optimistic, moderately optimistic, and pessimistic. For each profile, perceptions developed differently over time, with the moderately optimistic and pessimistic students being at risk in different ways. Results imply that expectations deserve a more prominent place when designing innovative learning environments.

Host cell proteins (HCPs) coexpressed during the production of biotherapeutics can affect the safety, efficacy, and stability of the final product. As such, monitoring HCP populations and amounts throughout the production and purification process is an essential part of the overall quality control framework. Mass spectrometry (MS) is used as an orthogonal method to enzyme-linked immunosorbent assays (ELISA) for the simultaneous identification and quantification of HCPs, particularly for the analysis of downstream processes. In this study, we present an MS-based analytical protocol with improvements in both speed and identification performance that can be implemented for routine analysis to support upstream process development. The protocol adopts a streamlined sample preparation strategy, combined with a high-throughput MS analysis pipeline. The developed method identifies and quantifies over 1000 HCPs, including 20 proteins listed as high risk in the literature, in a clarified cell culture sample with repeatability and precision shown for digest replicates. In addition, we explore the effects of varying standard spike-ins and changes to the data processing pipeline on absolute quantification estimates of the HCPs, which highlight the importance of standardization for wider use in the industry. Data are available via ProteomeXchange with the identifier PXD053035.

Hybrid yarns, combining stainless steel with glass fibers, are promising for impact-resistant composites. Inside the yarn, the thermoplastics matrix is provided in the form of endless filaments. Thermoplastics gained popularity as composites' matrix due to recyclability. The study emphasizes customizing adhesion between stainless steel and polypropylene for desired properties in the composites. Tailored adhesion is crucial for optimizing the performance of stainless steel/polypropylene composites. Within this contribution, a selection of adhesion promoters and preventers is analyzed to generate adjustable adhesion between polypropylene matrix and stainless steel filaments. The characterization is fulfilled using contact angle measurements on films of coating agents and coated stainless steel filaments. Furthermore, surface free energy is calculated and theoretical adhesion is analyzed between coating agent and stainless steel filaments and coated stainless steel filaments and polypropylene matrix. The results are validated by single fiber pullout tests.

In this work, the task of designing a building’s energy supply is studied. The problem is examined under the aspect of conflicting goals (monetary and environmental goals) and uncertainties. Uncertainties can lie in future prices of energy, e.g., gas and electricity.

The solid-state additive manufacturing (AM) process cold spraying (CS) offers advantageous properties such as melt-free near-net-shape part fabrication and high deposition rates. Compared to other metal-based AM processes such as the powder bed fusion of metals (PBF-LB/M) or directed energy deposition (DED) processes such as laser metal deposition (DED-LB), CS features lower part resolution. One solution to increase the achievable level of detail is spraying onto removable molds. No study exists that investigates the general feasibility and manufacturing boundaries, from which design guidelines could be derived. In this paper, the applicability of material extruded and thermally bonded polymer (MEX-TRB/P) shapes, which is especially suitable for flexible low-cost production of small batches, as molds for cold spray additive manufacturing (CSAM) is investigated. For this purpose, material extruded thermoplastics are examined regarding their suitability for the CS process. Furthermore, geometrical and thus constructive restrictions of this new approach “Cold Spray Forming” (CSF) are analyzed using an industry-relevant use case. It was shown that the feasibility of this approach could be determined by the material value hardness of the sprayed polymer substrates.

Pressure equipment poses a high risk of harming people and the environment in case of failure. They are, therefore, highly regulated by the Pressure Equipment Directive. To enable laser powder bed fusion of metals (PBF-LB/M) for the manufacturing of such components, component appearance and quality need to be characterized and qualified for each specific system. In this study, the surface roughness of wall structures out of austenitic stainless steel (316L) is investigated. Wall structure specimens were produced by four manufacturing systems on different PBF-LB/M machines and with different powder materials. Surface roughness of specimens are compared in the upskin and downskin areas in relation to different slope angles and wall thicknesses. Although different process setups, parameters and powder feedstocks have been used, similarities in the dependency of the surface roughness related to the slope angle and wall thickness can be observed. This work furthermore presents a mechanism-based analytical approach to predict system-specific surface roughness. Particularly, the analytical approach on the influence of slope angle on the surface roughness of the downskin areas has not been covered in publications about PBF-LB/M before. The results of this work enable the prediction of system-specific surface roughness, which is especially important for parts with downskin areas and hidden surfaces without the possibility of additional surface treatment.

Quasi-2D layered halide perovskites (quasi-2DLPs) have emerged as promising materials for photovoltaic (PV) applications owing to their advantageous bandgap for absorbing visible light and the improved stability they enable. Their charge transport mechanism is heavily influenced by the grain orientation of their crystals as well as their nanostructures, such as grain boundaries (GBs) and edge states─the formation of which is inevitable in polycrystalline quasi-2DLP thin films. Despite their importance, the impact of these features on charge transport remains unexplored. In this study, we conduct a detailed investigation on polycrystalline quasi-2DLP thin films and devices, carefully analyzing how grain orientation and nanostructures influence charge transport. Employing nondestructive atomic force microscopy (AFM) topography, along with transient absorption spectroscopy (TAS) and grazing-incidence wide-angle X-ray scattering (GIWAXS), we obtained significant insights regarding the phase purity, crystallographic information, and morphologies of these films. Moreover, our systematic investigation using AFM-based techniques, including Kelvin probe force microscopy (KPFM) and conductive AFM (c-AFM), elucidates the roles played by GBs and edge states in shaping charge transport behavior. In particular, the local band structure along the GBs and edge states within both vertical and parallel grains was found to selectively repel electrons and holes, thus facilitating charge carrier separation. These findings provide perspectives for the development of high-performance quasi-2DLP PV devices and highlight potential approaches that can leverage the intrinsic properties of quasi-2DLPs to advance the performance of perovskite solar cells.

This work investigates the aqueous solid–liquid system of l-aspartic acid (l-Asp)/l-glutamic acid (l-Glu) mixtures. These amino acids are well researched in literature. However, some studies indicate conflicting results regarding its solid phase behavior. Especially the formation of solid solutions and polymorphic forms of these acids are of interest. This study aims to clarify the phase behavior and attempts to explain the stabilization of polymorphs in l-Asp/l-Glu mixtures. For this, binary and ternary solubilities are determined to extend and validate data sets available in literature. High performance liquid chromatography and powder X-ray diffraction were used as analytical tools. For ternary l-Asp/l-Glu/water mixtures, ternary phase and distribution diagrams were exploited to provide proper graphical representation and interpretation. Further, nonequilibrium solid phases were produced by fast evaporative crystallization. At equilibrium, aqueous l-Asp/l-Glu mixtures exhibit a solubility maximum at 0.73 wt % l-Asp/1.14 wt % l-Glu. Interestingly, their respective polymorphs, which are unstable in the pure form, are stabilized in the presence of the other amino acid. Nonequilibrium investigation showed the formation of kinetic solid solutions between the α l-Asp and β l-Glu polymorphic forms. The stabilization of the normally unstable polymorphic forms, with as little as 0.31 wt % l-Asp and 0.23 wt % l-Glu, in mixtures can be explained with the less energetically favorable solid phase incorporation. This work successfully provides clarification to conflicting studies found in literature and shows how simple, well studied amino acid systems may exhibit complex and priorly unknown phase behavior.

Kalman filtering is a powerful approach to adaptive filtering for various problems in signal processing. The frequency-domain adaptive Kalman filter (FDKF), based on the concept of the acoustic state space, provides a unifying solution to the adaptive filter update and the related stepsize control. It was conceived for the problem of acoustic echo cancellation and, as such, is frequently applied in hands-free systems. This article motivates and briefly recapitulates the linear FDKF and investigates how it can be further supported by deep neural networks (DNNs) in various ways, specifically to overcome the challenges and limitations related to the usually required estimation of process and observation noise covariances for the Kalman filter. While the mere FDKF comes with very low computational complexity, its neural Kalman filter variants may deliver faster (re)convergence, better echo cancellation, and even exceed the FDKF in its excellent double-talk near-end speech preservation both under linear and nonlinear loudspeaker conditions. To provide a synopsis of the state of the art, this article contributes a comparison of a range of DNN-based extensions of FDKF in the same training framework and using the same data.

Ti-containing zeotypes, notably titanosilicalite-1 (TS-1), are prominent examples of heterogeneous catalysts that have found applications in selective oxidation processes with hydrogen peroxide. Despite extensive characterization studies including using various probe molecules to interrogate the nature and the local environment of Ti sites, their detailed structure (as well as reactivity) remains elusive. Here, we demonstrate that using low temperature 15N magic angle spinning (MAS) ssNMR spectroscopy of adsorbed pyridine on TS-1 combined with Ti K-edge XANES on a range of samples (dehydrated, hydrated, contacted with H2O2and pyridine) provides unique information regarding the Ti sites, highlighting their reactivity and dynamic nature. While dehydrated TS-1 shows only Lewis acid sites, the presence of H2O generates Brønsted acid sites, whose amount correlates with water loading. Moreover, the methodology─based on 15N ssNMR and Ti K-edge XANES─applied to a library of samples with various Ti-loadings and absence of extraframework TiO2also enables quantification of the amount of Lewis acid sites and to establish a structure–activity descriptor (ratio of pyridine adsorbed on silanols vs titanium). Complementary analysis including computational modeling reveals that the reaction of Ti sites with H2O generates an acidic bridging silanol Ti-(OH)-Si, upon hydrolysis of one Ti–O–Si linkage, where Ti expands its coordination from four to pentacoordinated according to XAS.

In this study, the continuous chiral inversion of an undesired but cheap and readily available enantiomer into a desired valuable target enantiomer via coupling enzymatic racemization with preferential crystallization is investigated and experimentally demonstrated. Two different process configurations for coupling a racemization fixed-bed reactor with enantioselective fluidized bed crystallization are first theoretically studied using a developed process model. The results suggest that coupling racemization with a two-stage enantioselective fluidized bed crystallization allows for efficient enzyme utilization. Subsequent experiments performed in pilot plant scale led to successful, efficient, and robust continuous chiral inversion. An attractive continuous chiral inversion was achieved with a productivity of about 25 g/L/h and chiral purities > 98%.

DNA double-strand break (DSB) repair by homologous recombination is initiated by DNA end resection, a process involving the controlled degradation of the 5′-terminated strands at DSB sites1,2. The breast cancer suppressor BRCA1–BARD1 not only promotes resection and homologous recombination, but it also protects DNA upon replication stress1,3–9. BRCA1–BARD1 counteracts the anti-resection and pro-non-homologous end-joining factor 53BP1, but whether it functions in resection directly has been unclear10–16. Using purified recombinant proteins, we show here that BRCA1–BARD1 directly promotes long-range DNA end resection pathways catalysed by the EXO1 or DNA2 nucleases. In the DNA2-dependent pathway, BRCA1–BARD1 stimulates DNA unwinding by the Werner or Bloom helicase. Together with MRE11–RAD50–NBS1 and phosphorylated CtIP, BRCA1–BARD1 forms the BRCA1–C complex17,18, which stimulates resection synergistically to an even greater extent. A mutation in phosphorylated CtIP (S327A), which disrupts its binding to the BRCT repeats of BRCA1 and hence the integrity of the BRCA1–C complex19–21, inhibits resection, showing that BRCA1–C is a functionally integrated ensemble. Whereas BRCA1–BARD1 stimulates resection in DSB repair, it paradoxically also protects replication forks from unscheduled degradation upon stress, which involves a homologous recombination-independent function of the recombinase RAD51 (refs. 4–6,8). We show that in the presence of RAD51, BRCA1–BARD1 instead inhibits DNA degradation. On the basis of our data, the presence and local concentration of RAD51 might determine the balance between the pronuclease and the DNA protection functions of BRCA1–BARD1 in various physiological contexts.

Recently, a new double-layer simulated moving bed (DL-SMB) process concept was introduced to separate continuously ternary or pseudoternary mixtures. The process exploits an operational similarity between SMB chromatography and fractional distillation using a dividing wall. There are well-established concepts for designing classical SMB processes that provide two outlet streams. However, for multicomponent and nonlinear isotherm systems, it is difficult to obtain an explicit solution for the short-cut design of the DL-SMB process. We introduce, in this work, an iterative short-cut design method for competitive Langmuir adsorption isotherms based on the triangle theory. For illustration and validation, three cycloketones (cycloheptanone, cyclohexanone, and cyclopentanone) were considered. Using a C18 column and water/acetonitrile mobile phases, the isotherm parameters and dispersion coefficients were experimentally measured. Applying these parameters, feasible operation conditions were identified by the proposed iterative short-cut design method. Performing numerical simulation using the equilibrium dispersion model, the operation conditions predicted by the proposed short-cut design method were validated successfully.

This article introduces. the concept and design of a planar magnetic regulator (PMR) integrated into a 260-W LLC resonant light-emitting diode driver for tunable white string. Utilizing low-profile magnetic cores and printed circuit board windings, the PMR effectively modulates the converter's magnetizing inductance. The article outlines a systematic design methodology for the PMR and its integration into the LLC converter to regulate the magnetizing inductance and consequently the output current. The implemented prototype exhibited zero voltage switching behavior across the entire power range and demonstrated precise control over the correlated color temperature. The PMR offers significant advantages, including enhanced power density, reduced skin effects, decreased current requirements, and a reduced need for turns in windings

Insomnie und exzessive Tagesschläfrigkeit sind in der Allgemeinbevölkerung die häufigsten Störungsbilder/Symptome aus dem Formenkreis der Schlaf-Wach-Störungen. Eine gezielte Anamnese und apparative Zusatzdiagnostik ermöglichen eine genauere ätiologische Zuordnung, wobei häufig zwei oder mehrere Schlafstörungen gleichzeitig vorliegen. Daraus ergeben sich multimodale individuelle Therapiekonzepte. Anhand von zwei Fallbeispielen werden typische Konstellationen zu den Themen Insomnie und zentrale Hypersomnolenzsyndrome beschrieben. Diese sollen das Bewusstsein für eine frühzeitige und möglichst exakte Diagnose schärfen, um Chronifizierung und fehlgeschlagene Therapieversuche hintanzuhalten.

Stall flutter, a fluid–structural interaction driven by dynamic stall, has primarily been studied as a two-dimensional flow phenomenon. However, recent investigations suggest that wing sweep, which induces spanwise flow and cross-flow instability, significantly influences the leading-edge vortex (LEV) formation. This paper investigates the effects of wing sweep on stall flutter instabilities using a cyber-physical approach, combining experiments and high-fidelity simulations. Results reveal that increasing sweep reduces flutter amplitude and delays instability onset by weakening the LEV. The spanwise flow induced by sweep promotes LEV shedding and breakdown, leading to a stabilizing effect. Prescribed and responding motions exhibit similar dynamics, with minor differences attributed to nonlinearities in the fluid–structure interaction. Detailed analysis of the flow field and unsteady aerodynamic forces provides insights into the complex interplay between sweep, LEV development, and aeroelastic stability.

In obstetric clinics in Berlin, Germany, more than half of the women are immigrants. The main objective of the qualitative study was to explore the staff’s experiences with obstetric care for immigrants and juxtapose it with the immigrants’ comments on their birth experiences. We analyze potential differences along the framework of a cultural health capital (CHC). Between May and August 2017, semi-structured interviews were carried out with 17 obstetricians and 17 midwives at four obstetric clinics in Berlin. The verbally transcribed interview material was subjected to a qualitative content analysis according to Mayring. Furthermore, a secondary data from an interview study was analyzed in the purpose of providing some insight into the practitioner study participant perspective. Between January and May 2017, in the postpartum ward at the Berlin Charité Campus Virchow Clinic, an interview study guided by the migrant-friendly maternity care questionnaire was conducted among 410 migrant and non-migrant women. For this study, the free-text comments on the pregnancy care were analyzed. The staff interviewees identified language barrier and legal status as risk factors for the late onset of obstetric care. CHC functioning potentially as alternatives to the established health care structures were voiced. Strong family ties among immigrant families bear a high potential for support. Gratefulness was voiced by the staff and immigrant patients as a source of satisfaction with care. Our study shows that obstetric care for immigrant women remains a challenge. CHC of immigrant women might partially compensate for exclusion.

Alkyl radicals generated via an acridine photocatalyzed decarboxylation reaction of feedstock carboxylic acids engage with a range of cyclic imine–BF3complexes to provide α-functionalized azacycles in an operationally simple process. A three-component variant of this transformation incorporating [1.1.1]propellane as an additional reaction partner enables the synthesis of valuable bicyclopentane (BCP)-containing azacycles. Reactions exhibit good functional group compatibility, enabling late-stage modification of complex bioactive molecules.

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This work focuses on the growth of GeSn p-n-p hetero bipolar phototransistors (HPT) with a Sn content of 6% and a Ge reference bipolar phototransistor. The devices were grown on Ge virtual substrates on Si using molecular beam epitaxy. The transistors were created as two-terminal devices with a free-floating base. Based on the electro-optical analysis, it is evident that the GeSn HPT performs much more effectively in inverse operation compared to regular operating mode. This seems to be attributed to the band offsets. The GeSn HPT's photoresponse does not show a linear correlation with the incident optical power. It has been discovered that the power law factor is less than one, resulting in a noticeably greater amplification of the photocurrent at low optical powers. At a wavelength of 1550 nm and an optical power of 0 dBm, our fabricated GeSn HPT achieves an optical responsivity of 1.5 A/W, which is significantly higher than most of the previously reported values. These findings pave the way for further advancements in high-performance GeSn HPT for optical communication applications.