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Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P< .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P= .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Strong field ionization of molecules by intense laser pulses can be simulated by time-dependent configuration interaction (TD-CI) with a complex absorbing potential (CAP). Standard molecular basis sets need to be augmented with several sets of diffuse functions for effective interaction with the CAP. This dramatically increases the number of configurations and the cost of the TD-CI simulations as the size of the molecules increases. The cost can be reduced by making use of spin symmetry and by employing an orbital energy cutoff to limit the number of virtual orbitals used to construct the excited configurations. Greater reductions in the number of virtual orbitals can be obtained by examining their interaction with the absorbing potential during simulations and their contributions to the strong field ionization rate. This can be determined from the matrix elements of the absorbing potential and the TD-CI coefficients from test simulations. Compared to a simple 3 hartree cutoff in the orbital energies, these approaches reduce the number of virtual orbitals by 20–35% for neutral molecules and 5–10% for cations. As a result, the cost of simulations is reduced by 35–60% for neutral molecules. The number of virtual orbitals needed can also be estimated by second-order perturbation theory without the need for test simulations. The number of virtual orbitals can be reduced further by adapting orbitals to the laser field using natural orbitals derived from test simulations. This is particularly effective for cations, yielding reductions of more than 20%.

This article provides a brief overview on THz communications and subsequently focuses on the application of 300 GHz backhaul and fronthaul links. The fundamentals, planning, and software simulation approaches as well as the realized bidirectional 300 GHz demonstrator built within the Horizon 2020 joint EU-Japan project ThoR are described. The ThoR demonstrator uses off-the-shelf modems for network connections and baseband processing, RF front-ends based on InGaAs mHEMT technology and a spurious-free/low-phase noise photonic solution for LO generation. With the ThoR set-up, a net data rate of 2 × 20 Gbps over a distance of 150 m using a total instantaneous bandwidth of 8.64 GHz has been demonstrated. It is also shown that the IEEE Std 802.15.3-2023 protocol works correctly for this application.

We propose a novel approach to joint sensing and communications based on the use of spectrally sparse sensing waveforms combined with standard communications signals. Efficient spectrum utilization in wireless networks is becoming more important as the number of wireless systems increases dramatically, leading to challenges in sensing the environment without impacting communication throughput. Our approach is based on the use of a spectrally efficient sensing waveform that provides near-optimal ranging accuracy while occupying a very small spectral footprint. The sensing waveform consists of two discrete tones, the separation of which, along with the signal-to-noise ratio, determines the ranging accuracy. The spectral space between the two tones is not utilized for sensing and can thus be occupied with communications data, with negligible impact on data throughput or sensing accuracy. We implement a 40-MHz binary phase shift keyed (BPSK) waveform with ranging tones placed at ±80 MHz, in the second nulls of the data spectrum, at a carrier frequency of 4 GHz using an arbitrary waveform generator. We demonstrate the ability to track the motion of a walking person in an indoor environment and the locations of two people in an outdoor environment. Measured range standard deviations were 1.3 mm for a corner reflector in a semi-anechoic chamber and were 12 and 15 mm for the two-person outdoor case.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.

We provide an approach to sample rare events during classical ab initio molecular dynamics and quantum wavepacket dynamics. For classical AIMD, a set of fictitious degrees of freedom are introduced that may harmonically interact with the electronic and nuclear degrees of freedom to steer the dynamics in a conservative fashion toward energetically forbidden regions. A similar approach when introduced for quantum wavepacket dynamics has the effect of biasing the trajectory of the wavepacket centroid toward the regions of the potential surface that are difficult to sample. The approach is demonstrated for a phenol-amine system, which is a prototypical problem for condensed phase-proton transfer, and for model potentials undergoing wavepacket dynamics. In all cases, the approach yields trajectories that conserve energy while sampling rare events.

Purpose: In recent years, the robotic process automation (RPA) technology has increasingly been used to automate business processes. While a lot of research has been published on the potential and benefits of the technology, only a few studies have conducted research on challenges related to RPA adoption. Hence, this study aims to identify and discuss challenges related to RPA implementation projects. Design/methodology/approach: Following an inductive methodology, interviews have been conducted with consultants who were involved in multiple RPA implementation projects. Hence, their extensive experience and views contribute to a detailed and in-depth understanding of the phenomena under research. Findings: The results suggest that there are various process-related, technical, resource-related, psychological and coordinative challenges that must be considered when conducting an RPA implementation project. Originality/value: This paper contributes to knowledge by presenting a new typology of challenges, as well as providing an in-depth discussion of the individual challenges that organizations face.

The Sharpless reaction is an enantioselective epoxidation of prochiral allylic alcohols that employs a Ti(IV) catalyst formed from titanium tetra(isopropoxide), Ti(O-i-Pr)4, diethyl tartrate (DET), and the oxidizing agent tert-butyl hydroperoxide. The M06-2X DFT functional with the 6-311+G(d,p) basis set has been employed to model the structures and energetics of the Sharpless epoxidation reaction. The monomeric tetracoordinate titanium(IV) diethyltartrate is thermodynamically strongly favored to dimerize, producing a pentacoordinate catalyst, [Ti(DET)(O-i-Pr)2]2, that is a more reactive chiral epoxidation catalyst. The rapid ligand exchange reactions needed to generate the “loaded” catalyst and to repeat the overall catalytic cycle have been examined and are found to have activation energies that are much lower than the epoxidation barriers. The transition structures and activation energies for the enantioselective epoxidation of allyl alcohol, trans-methyl-allyl alcohol and trans-tert-butyl-allyl alcohol with the “loaded” Sharpless catalyst, [Ti2(DET)2(O-i-Pr)2-(OAllyl)-(OOt-Bu)], are presented. The effect of the C═O···Ti interactions on the activation energies and the significance of the O–C–C═C dihedral angle on the enantioselectivity of the epoxidation reaction are discussed.

The structural diversity of different lipid species within the membrane defines its biophysical properties such as membrane fluidity, phase transition, curvature, charge distribution, and tension. Environment-sensitive probes, which change their spectral properties in response to their surrounding milieu, have greatly contributed to our understanding of such biophysical properties. To realize the full potential of these probes and avoid misinterpretation of their spectral responses, a detailed investigation of their fluorescence characteristics in different environments is necessary. Here, we examined the fluorescence lifetime of two newly developed membrane order probes, NR12S and NR12A, in response to alterations in their environments such as the degree of lipid saturation, cholesterol content, double bond position and configuration, and phospholipid headgroup. As a comparison, we investigated the lifetime sensitivity of the membrane tension probe Flipper in these environments. Applying fluorescence lifetime imaging microscopy (FLIM) in both model membranes and biological membranes, all probes distinguished membrane phases by lifetime but exhibited different lifetime sensitivities to varying membrane biophysical properties (e.g., cholesterol). While the lifetime of Flipper is particularly sensitive to the membrane cholesterol content, the NR12S and NR12A lifetimes are moderately sensitive to both the cholesterol content and lipid acyl chains. Moreover, all of the probes exhibit longer lifetimes at longer emission wavelengths in membranes of any complexity. This emission wavelength dependency results in varying lifetime resolutions at different spectral regions, which are highly relevant for FLIM data acquisition. Our data provide valuable insights on how to perform FLIM with these probes and highlight both their potential and limitations.

Purpose: Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting. Methods: Different MVs were installed in the simulator, and pressure, flow, and transesophageal echocardiographic measurements were obtained. To confirm the simulator’s physiological range, we first installed a biological prosthetic, a mechanical prosthetic, and a competent excised porcine MV. Subsequently, we inserted two porcine MVs—one with induced chordae tendineae rupture and the other with a dilated annulus, along with a patient-specific silicone valve extracted from echocardiography with bi-leaflet prolapse. Finally, TEER and MIMVS procedures were conducted by experts to repair the MVs. Results: Systolic pressures, cardiac outputs, and regurgitations volumes (RVol) with competent MVs were 119 ± 1 mmHg, 4.78 ± 0.16 l min−1, and 5 ± 3 ml respectively, and thus within the physiological range. In contrast, the pathological MVs displayed increased RVols. MIMVS and TEER resulted in a decrease in RVols and mitigated the severity of mitral regurgitation. Conclusion: Ex-vivo modelling of MV pathologies and repair procedures using the described simulator realistically replicated physiological in-vivo conditions. Furthermore, we showed the feasibility of performing MIMVS and TEER at the simulator, also at patient-specific level, thus providing new clinical perspectives in terms of training modalities and personalized planning.

To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction.

Zusammenfassung: Traumatisch bedingte Fehlstellungen des Augapfels wie Enophthalmus und Bulbustiefstand beeintr�chtigen den Patienten in Bezug auf Funktion und �sthetik. Die exakte Einstellung der Bulbusposition ist Voraussetzung f�r ein doppelbildfreies Sehen und ein unauff�lliges Erscheinungsbild der Augenpartie. Es ist das Ziel des Fallberichtes zu zeigen, wie ein computerassistiertes, nicht ionisierendes, ber�hrungsfreies, intraoperativ anwendbares, optisches 3D-Verfahren zur Bestimmung der Bulbuslage die Einstellung des Augapfels in die gew�nschte Position bei komplexen Orbitarekonstruktionen unterst�tzt. Ein 33-j�hriger Mann stellte sich vor, weil der rechte Augapfel zusehends in die Augenh�hle zur�cksank. Sechs Monate zuvor wurde alio loco eine rechtsseitige zentrolaterale Mittelgesichtsfraktur mit Orbitabodenbeteiligung versorgt. Das konsekutiv aufgetretene Doppelbildsehen und die auff�llige Fehlstellung des rechten Auges beeintr�chtigten den Patienten. Zur Planung der Korrektur der Position des rechten Bulbus wurde zun�chst ein 3-dimensionales Bild der Gesichtsoberfl�che bei ge�ffneten Augen mit einem optischen Sensor erstellt. In einem automatisierten Symmetrievergleich ergab sich f�r die relative En- und Exophthalmometrie ein rechtsseitiger Enophthalmus von 4 mm. Es wurde die Entscheidung getroffen, den rechten Orbitaboden mit einem Sch�delkalottentransplantat anzuheben. Intraoperativ erfolgte die Kontrolle der Bulbusposition ebenfalls mit dem optischen 3D-Verfahren. Am Ende des Eingriffs ergab sich in der relativen En- und Exophthalmometrie ein Exophthalmus von 1 mm auf der rechten Seite. Sechs Wochen postoperativ beklagte der Patient keine Doppelbilder mehr. Nach 3 und nach 24 Monaten bestand rechts ein Enophthalmus von 1 mm. Der Fallbericht verdeutlicht, wie das computerassistierte, nicht ionisierende, ber�hrungsfreie, optische 3D-Verfahren Planung, intraoperative Umsetzung und Verlaufskontrolle bei der Korrektur der Bulbusposition unterst�tzen und so als hilfreiches Werkzeug bei komplexen Rekonstruktionen der Orbita dienen kann.

Zusammenfassung: Hintergrund: Die Revision einer gelockerten und migrierten Pfannenkomponente mit Knochenverlust im Rahmen der Hüftendoprothetik stellt eine große chirurgische Herausforderung dar. Ziel sollte eine funktionell günstige Rekonstruktion des Rotationszentrums bei suffizienter, mechanischer Belastbarkeit des Acetabulums sein. Die diesbezüglich in Europa am häufigsten eingesetzten Revisionsimplantate sind die Müller-Abstützschale, die Hakendachschale nach Ganz, sowie der Burch-Schneider-Ring. Patienten und Methoden: Wir berichten über unsere Erfahrungen mit diesen Implantaten bei 298 Patienten (298 Hüften) und einer medianen Nachuntersuchungszeit von 4 (0–17) Jahren im Rahmen einer retrospektiven Studie. Ergebnisse: Von 224 Patienten (75%) konnten Nachuntersuchungsdaten erhoben werden. Hierbei wurde bei 176 Patienten (59%) eine radiologische Untersuchung durchgeführt. Weiterhin waren 54 Patienten (18%) verstorben, von 3 Patienten (1%) konnten keine Daten erhoben werden. Bei 18 Patienten (6%) wurde im Nachbeobachtungszeitraum eine erneute Revision durchgeführt, davon war in 9 Fällen die Ursache eine aseptische Lockerung, bei den übrigen 9 Fällen eine septische Lockerung. In 7 weiteren Fällen (2%) wurde im Rahmen der Nachuntersuchung ein radiologisches und klinisches Versagen des Implantats diagnostiziert. Die Überlebensrate nach 5 Jahren betrug 94% bzw. 89% nach 8 Jahren. Schlussfolgerung: Die Revision mit Abstützschalen führt zu akzeptablen, mittelfristigen Ergebnissen. Hauptsorgenpunkte bilden die septischen Komplikationen sowie das lytische Versagen des Spongiosatransplantats mit konsekutiver Lockerung des Abstützrings.

Targeting AML by chimeric antigen receptor T-cells (CAR-T) is challenging due to the promiscuous expression of AML-associated antigens in healthy hematopoiesis and high degree of inter- and intratumoral heterogeneity. Here, we present single-cell expression data of AML-associated antigens in 30 primary pediatric AML samples. We identified CD33, CD38, CD371, IL1RAP and CD123 as the most frequently expressed. Notably, high variability was observed not only across the different patient samples but also among leukemic cells of the same patient suggesting the necessity of multiplexed targeting approaches. To address this need, we utilized our modular Adapter CAR (AdCAR) platform, enabling precise qualitative and quantitative control over CAR-T-cell function. We show highly efficient and target-specific activity for newly generated adapter molecules (AMs) against CD33, CD38, CD123, CD135 and CD371, both in vitro and in vivo. We reveal that inherent intratumoral heterogeneity in antigen expression translates into antigen escape and therapy failure to monotargeted CAR-T therapy. Further, we demonstrate in PDX models that rational combinatorial targeting by AdCAR-T-cells can cure heterogenic disease. In conclusion, we elucidate the clinical relevance of heterogeneity in antigen expression in pediatric AML and present a novel concept for precision immunotherapy by combinatorial targeting utilizing the AdCAR platform.

Abstract.The ability to recognize other people’s emotions from their face, voice, and body (emotion recognition ability, ERA) is crucial to successful functioning in private and professional life. The Geneva Emotion Recognition Test (GERT; Schlegel, Grandjean, & Scherer, 2014) is a new instrument to measure ERA in a more ecologically valid way than previous tests. In this article, we report the results of five studies examining the test’s construct validity with a total Nof 1,284. We found that the GERT was highly positively correlated with other performance-based tests measuring ERA and emotional intelligence (EI), as well as with cognitive intelligence. GERT scores were also related to higher self-reported empathy, openness, and neuroticism, and to better social adjustment. Furthermore, higher GERT scores were related to lower anxiety, anger expressivity, and alexithymia. In line with previous findings, women scored higher than men and GERT performance declined with increasing age. Taken together, these results provide considerable evidence for the construct validity of the GERT and for ERA as an adaptive skill that likely facilitates better life outcomes.

Undetected partial discharges (PDs) are a safety critical issue in high voltage (HV) gas-insulated systems (GIS). While the diagnosis of PDs under AC voltage is well-established, the analysis of PDs under DC voltage remains an active research field. A key focus of these investigations is the classification of different PD sources to enable subsequent sophisticated analysis. In this paper, we present an analysis of a 1D-CNN-based approach for classifying laboratory PD signals caused by metallic protrusions and conductive particles on the insulator of HVDC GIS, under both negative and positive potentials. Most notably, our study demonstrates that this type of neural network, regardless of the training order, can generalize learnings to operating voltage multiples that it has not previously encountered. We evaluate this generalization performance under the presence of additional white Gaussian noise and investigate the influence of excluding the amplitude-related information in the signal. Further, we compare the network's performance when using input signals in both the time and frequency domain.

For how long the nutrient supply from long‐term application of manure and swine effluent will last to sustain crop production after applications had ceased is a research gap. We quantified the change in soil chemical properties 12 years after cattle manure and swine effluent applications had ceased. Data were collected in 2008 (termination of applications) and 2020 on a long‐term animal waste study at the Kansas State University, Southwest Research‐Extension Center near Tribune, KS. Treatments were three levels of cattle manure and swine effluent (phosphorus, P; nitrogen, N; and 2N) and an untreated control. Soil profile NO3‐N declined 78%–95%, 70%–82%, and 58% from the initial amount in 2008 compared to the amount remaining in 2020 in the swine effluent, cattle manure, and an untreated check, respectively. Profile NO3‐N levels were greatly elevated by the P‐based swine effluent treatment and the 2N rate of both cattle manure and swine effluent and remained high (>250 kg ha−1) after 12 years. Total nitrogen in the surface soil decreased by 11%–27% for cattle manure treatments with little change in the swine effluent and check treatments. Total carbon concentration in the surface soil decreased from 22% to 31% for cattle manure treatments and from 7% to 14% for swine effluent and check treatments. Mehlich‐3 P decreased significantly for the cattle manure treatments (41%–53%) but still remained very high (>100 mg kg−1). Soil test P levels in the swine treatments were similar to the check treatment. Application of cattle manure and swine effluent has lasting effects on many soil chemical properties long after ceasing applications. Twelve years after treatment withdrawal, NO3‐N in profile decreased by 70%–82%, 78%–95%, and 58% from cattle manure, swine effluent, and check treatments, respectively.Total carbon concentration decreased 22%–31% for cattle manure and 7%–14% for swine effluent and check treatments.Mehlich‐3 P decreased by 41%–53% for cattle manure, 36%–58% for swine effluent, and 35% for the check.Cattle manure treatments continued to have high levels of soil test P 12 years after the last application.Application of swine effluent based on P requirement resulted in a buildup of NO3‐N which persisted for 12 years.

AbstractThe Euler-Euler model is widely used in bubbly flow simulations up to industrial dimensions. The standard Euler-Euler model is based on the phase-averaging method. After averaging, the bubble forces in the field equations are functions of the local void fraction. In simulations, when the bubble diameter is larger than the computational cell spacing, the forces can transport the gas belonging to the same bubble in different directions. By contrast, a closure model for the bubble force is typically developed based on the assumption that the force is a resultant force that acts on the bubble’s center of mass. This inconsistency can lead to a nonphysical gas concentration in the center of a channel or near the channel wall if the bubble diameter is larger than the cell spacing. The purpose of the present contribution is to develop an Euler-Euler model where the bubble force consistency is recovered for two-phase flow simulations where the diameter of the disperse phase can be larger than the cell spacing. Such an Euler-Euler model is developed by combining an existing particle-center-averaged Euler-Euler framework with a Gaussian convolution method. To validate this Euler-Euler approach, a comparison is made with experimental data for the bubbly flows in two different vertical pipes. The results show that the proposed Euler-Euler model recovers the bubble force consistency and alleviates the overprediction of the void fraction peak near the wall, while its simulation results in the axial gas and liquid velocity and the liquid turbulence kinetic energy are similar to the results of the standard Euler-Euler model.

AbstractIndustrial multiphase flows are typically characterized by coexisting morphologies. Modern simulation methods are well established for dispersed [e.g., Euler-Euler (E-E)] or resolved [e.g., volume-of-fluid (VOF)] interfacial structures. Hence, a morphology adaptive multifield two-fluid model is proposed that is able to handle dispersed and resolved interfacial structures coexisting in the computational domain with the same set of equations. An interfacial drag formulation for large interfacial structures is used to describe them in a VOF-like manner. For the dispersed structures, the baseline model developed at Helmholtz-Zentrum Dresden-Rossendorf is applied. The functionality of the framework is demonstrated by investigating a single rising gas bubble in a stagnant water column, a two-dimensional stagnant stratification of water and oil sharing a large-scale interface that is penetrated by micro gas bubbles, and an isothermal countercurrent stratified flow case. Recent developments focus on the transition region, where bubbles are overresolved or underresolved either for E-E or for VOF. Furthermore, a concept is presented for the transition of oversized dispersed bubbles into the resolved phase.

Dieser Artikel beschreibt den finalen Aufbau und das Funktionsprinzip der neuen 5 MN·m Drehmoment-Normalmesseinrichtung (Dm-NME) der Physikalisch-Technischen Bundesanstalt (PTB). Die Maschine ist für mechanische Mehrkomponentenbelastung ausgelegt und kann neben dem Drehmoment, eine Axialkraft, Biegemomente und Querkräfte auf den Prüfling übertragen. Das Design der Maschine ist so optimiert, daß die Einflüsse parasitärer Komponenten auf das Hauptdrehmoment weitgehend reduziert werden.

Converting glucose electrochemically to its valuable derivatives, gluconic and glucaric acids, is a promising process for the utilization of renewable carbon sources. Understanding the reaction pathway to form glucaric acid from glucose is key to performing the process efficiently. In this study, we investigate the influence of mass transport as well as electrode potential on the product distribution in glucose, gluconic acid, and glucuronic acid oxidation on a gold disk in an RDE setup. We find glucose and glucuronic acid to be easily oxidized, while the oxidation of gluconic acid is kinetically limited. Combining DFT calculations and the experimental results, we show that on gold, the oxidation of aldehyde groups proceeds readily, while the oxidation of hydroxyl groups is challenging and occurs indiscriminately on C atoms in glucose and its derivatives. Additionally, the DFT calculations present a reaction pathway that can explain the absence of glucuronic acid in the conducted experiments.

Asymmetric reactions that convert racemic mixtures into enantioenriched amines are of significant importance due to the prevalence of amines in pharmaceuticals, with about 60% of drug candidates containing tertiary amines. Although transition-metal catalyzed allylic substitution processes have been developed to provide access to enantioenriched α-disubstituted allylic amines, enantioselective synthesis of sterically demanding α-tertiary amines with a tetrasubstituted carbon stereocenter remains a major challenge. Herein, we report a chiral diene-ligated rhodium-catalyzed asymmetric substitution of racemic tertiary allylic trichloroacetimidates with aliphatic secondary amines to afford α-trisubstituted-α-tertiary amines. Mechanistic investigation is conducted using synergistic experimental and computational studies. Density functional theory calculations show that the chiral diene-ligated rhodium promotes the ionization of tertiary allylic substrates to form both antiand synπ-allyl intermediates. The antiπ-allyl pathway proceeds through a higher energy than the synπ-allyl pathway. The rate of conversion of the less reactive π-allyl intermediate to the more reactive isomer via π–σ–π interconversion was faster than the rate of nucleophilic attack onto the more reactive intermediate. These data imply that the Curtin–Hammett conditions are met in the amination reaction, leading to dynamic kinetic asymmetric transformation. Computational studies also show that hydrogen bonding interactions between β-oxygen of allylic substrate and amine-NH greatly assist the delivery of amine nucleophile onto more hindered internal carbon of the π-allyl intermediate. The synthetic utility of the current methodology is showcased by efficient preparation of α-trisubstituted-α-tertiary amines featuring pharmaceutically relevant secondary amine cores with good yields and excellent selectivities (branched–linear >99:1, up to 99% enantiomeric excess).

CFD models (turbulent models and interfacial forces) incorporated with the population balance model (PBM) have been validated, azimuthally, with the gamma-ray-computed tomography (CT) results to address the effect of the presence of internals with different arrangements and diameters. The superficial gas velocity applied was varied from 0.05 to 0.45 m/s. The results exhibit the capability to predict the hydrodynamics of the bubble column, further incorporating the population balance model and promoting the prediction of simulation in high superficial gas velocity. The effect of internals revealed that the gas holdup was significantly enhanced in the bubble column’s wall region, while the gas holdup was increased remarkably in the center and the wall regions of the bubble column equipped by internals of 1 in. diameter more than in internals of 0.5 in. However, internals with a hexagonal arrangement increase the gas holdup in the central region and less in the wall than in the circular arrangement.

AbstractIn >100,000 observations across Swiss acute-care hospitals, hand hygiene (HH) adherence significantly increased during the first coronavirus disease 2019 (COVID-19) wave. However, despite persisting COVID-19 activity, HH adherence returned to prepandemic levels over a 2-year observation period. These results indicate that training and support remains challenging.

Zusammenfassung: Wir fordern eine Absicherung aller Sichteinlagen. Jederzeit kündbare, aber ungesicherte Depositen sind der Hauptgrund für Bankenruns. Deren Geschwindigkeit und Ansteckungsrisiken sind durch Digitalisierung und soziale Medien stark gestiegen. Wir argumentieren, dass Bankenruns, die traditionell als Instrument der Risikobegrenzung gesehen werden, diese Aufgabe aufgrund der impliziten Staatsgarantie bei potenziell systemischen Risiken heute nicht mehr leisten können. Stattdessen wurde in Europa eine eigene Klasse von Schuldinstrumenten geschaffen, sogenannte Bail-in Anleihen, die in einem geregelten Rahmen Marktdisziplin sicherstellen sollen. Für die Moral Hazard Begrenzung bieten MREL und Kosten der Einlagensicherung Gestaltungsmöglichkeiten. Wir erläutern unseren Vorschlag und gehen auf zahlreiche Gegenargumente ein, die in der öffentlichen Diskussion vorgebracht wurden.

Various soil health indicators that measure a chemically defined fraction of nitrogen (N) or a process related to N cycling have been proposed to quantify the potential to supply N to crops, a key soil function. We evaluated five N indicators (total soil N, autoclavable citrate extractable N, water‐extractable organic N, potentially mineralizable N, and N‐acetyl‐β‐D‐glucosaminidase activity) at 124 sites with long‐term experiments across North America evaluating a variety of managements. We found that 59%–81% of the variation in N indicators was among sites, with indicator values decreasing with temperature and increasing with precipitation and clay content. The N indicators increased from 6%–39% in response to decreasing tillage, cover cropping, retaining residue, and applying organic sources of nutrients. Overall, increasing the quantity of organic inputs, whether from increased residue retention, cover cropping, or rotations with higher biomass, resulted in higher values of the N indicators. Although N indicators responded to management in similar ways, the analysis cost and availability of testing laboratories is highly variable. Further, given the strong relationships of the N indicators with carbon (C) indicators, measuring soil organic C along with 24‐h potential C mineralization could be used as a proxy for N supply instead of measuring potentially mineralizable N or any other N indicator directly. Nitrogen indicators of soil health vary predictably across North America with climate and soil texture.The response to soil health practices is similar across all indicators.There are strong correlations among nitrogen indicators, but also between carbon and nitrogen indicators.Soil organic carbon and 24‐h carbon mineralization potential can be used to capture nitrogen cycling.

Health care has forever changed in early 2021. Three years after the beginning of the COVID-19 world pandemic, we must seriously look at the role of the nurses and the model we deploy to ensure our health system's viability. In this article, the authors offer insights into the journey of deconstructing the nurses' role and planning for a Co-Caring Model where virtual and bedside nurses practice and unlicensed assisting personnel work as a team to care for those in need of health care. We also provide a list of actions for nurse leaders to consider. Finally, we aim to spark an international conversation on how we can bring back the joy of practice to ensure we create the best possible places to give and get care.

Centromeres are critical for cell division, loading CENH3 or CENPA histone variant nucleosomes, directing kinetochore formation and allowing chromosome segregation1,2. Despite their conserved function, centromere size and structure are diverse across species. To understand this centromere paradox3,4, it is necessary to know how centromeric diversity is generated and whether it reflects ancient trans-species variation or, instead, rapid post-speciation divergence. To address these questions, we assembled 346 centromeres from 66 Arabidopsis thalianaand 2 Arabidopsis lyrataaccessions, which exhibited a remarkable degree of intra- and inter-species diversity. A.thalianacentromere repeat arrays are embedded in linkage blocks, despite ongoing internal satellite turnover, consistent with roles for unidirectional gene conversion or unequal crossover between sister chromatids in sequence diversification. Additionally, centrophilic ATHILAtransposons have recently invaded the satellite arrays. To counter ATHILAinvasion, chromosome-specific bursts of satellite homogenization generate higher-order repeats and purge transposons, in line with cycles of repeat evolution. Centromeric sequence changes are even more extreme in comparison between A.thalianaand A.lyrata. Together, our findings identify rapid cycles of transposon invasion and purging through satellite homogenization, which drive centromere evolution and ultimately contribute to speciation.

Speed is key during infectious disease outbreaks. It is essential, for example, to identify critical host binding factors to pathogens as fast as possible. The complexity of host plasma membrane is often a limiting factor hindering fast and accurate determination of host binding factors as well as high-throughput screening for neutralizing antimicrobial drug targets. Here, we describe a multiparametric and high-throughput platform tackling this bottleneck and enabling fast screens for host binding factors as well as new antiviral drug targets. The sensitivity and robustness of our platform were validated by blocking SARS-CoV-2 particles with nanobodies and IgGs from human serum samples.

In two studies, we tested how the expression of civic hope in narratives and the perceived authenticity of civic/political actions relate to civic/political engagement. In a cross-sectional study of undergraduates (N= 230), the expression of civic hope predicted the perceived authenticity of civic actions (e.g., voting), which in turn predicted the motivation to engage in them. In a longitudinal on-line study that began 8 weeks prior to the 2020 U.S. Presidential election (N= 308 MTurk workers), overall expressions of civic hope positively predicted the perceived authenticity of voting and the motivation to vote. In addition, expressions of civic hope positively predicted the perceived authenticity of voting, which in turn positively predicted the likelihood of reporting that one did vote. These findings indicate that a sense of civic hope and the experience of authenticity in political contexts may be important for democratic engagement.

For sustainable productivity, a winter wheat (Triticum aestivumL.)–summer crop (corn [Zea maysL.] or grain sorghum [Sorghum bicolorL.])–fallow (W‐SC‐F) cropping system could benefit from optimal wheat stubble cutting height management, but only limited information is available. The objective of this study was to evaluate the effect of wheat stubble height on subsequent corn and grain sorghum yields, available soil water, crop water use, and precipitation storage efficiency in a W‐C‐F and W‐S‐F cropping system. This study was conducted from 2006 through 2020 at the Kansas State University Southwest Research‐Extension Center near Tribune, KS. The experimental design was a randomized complete block with three wheat stubble heights (high, low, and strip). Average across all years, there was a 9%–10% corn yield and 7%–11% corn biomass advantage from high and stripper harvested wheat stubble compared with low cut stubble, and a 5% sorghum yield advantage from high cut stubble compared with low cut stubble. Kernel weight of corn was the only yield component that significantly differed among stubble height treatments. Water productivity of corn in the high and stripper harvested stubble treatments (15.3 kg ha−1mm−1) was significantly greater compared with the low cut stubble (14 kg ha−1mm−1). Water productivity of sorghum in the high cut stubble treatment (18.9 kg ha−1mm−1) was also significantly greater compared with low cut stubble (17.7 kg ha−1mm−1). Total available soil water at planting (ASWP) and available soil water at harvest (ASWH) of corn were both greater for high cut stubble compared with stripper harvested stubble but total ASWP and ASWH of grain sorghum were not significantly different among stubble height treatments. We concluded that low cut wheat stubble decreased subsequent corn and grain sorghum yields in a W‐C/S‐F cropping system. There was a 9%–10% corn yield and 7%–11% biomass advantage from high and stripper harvested compared with low cut wheat stubble.There was a 5% sorghum yield increase from high cut stubble compared with low cut wheat stubble.Kernel weight of corn was the only yield component that significantly differed in response to wheat stubble height.Water productivity of corn and sorghum in the high and stripper harvested was significantly greater compared with low cut wheat stubble.

Open-source environments such as the Computational Fluid Dynamics software OpenFOAM are very appealing for research groups since they allow for an efficient prototyping of new models or concepts. However, for downstream developments to be sustainable, i.e. reproducible and reusable in the long term, a significant amount of maintenance work must be accounted for. To allow for growth and extensibility, the maintenance work should be underpinned by a high degree of automation for repetitive tasks such as build tests, code deployment and validation runs, in order to keep the focus on scientific work. Here, an information technology environment is presented that aids the centralized maintenance of addon code and setup files with relation to reactor coolant system safety research. It fosters collaborative developments and review processes. State-of-the-art tools for managing software developments are adapted to meet the requirements of OpenFOAM. A flexible approach for upgrading the underlying installation is proposed, based on snapshots of the OpenFOAM development line rather than yearly version releases, to make new functionality available when needed by associated research projects. The process of upgrading within so-called sprint cycles is accompanied by several checks to ensure compatibility of downstream code and simulation setups. Furthermore, the foundation for building a validation data base from contributed simulation setups is laid, creating a basis for continuous quality assurance.

The extraction of objects from large-scale historical maps has been examined in several studies. With the aim to research urban changes over time, semi-automated and transferable holistic approaches remain to be investigated. We apply a combination of object-based image analysis and vectorization methods on three different historical maps. By further matching and georeferencing an appropriate current geodataset, we provide a concept for analyzing and comparing those valuable sources from the past. With minor adjustments, our end-to-end workflow was transferable to other large-scale maps. The findings revealed that the extraction and spatial assignment of objects, such as buildings or roads, enable the comparison of maps from different times and form a basis for further historical analysis. Performing an affine transformation between the datasets, an absolute offset of no more than 72 m was achieved. The outcomes of this paper, therefore, facilitate the daily work of urban researchers or historians. However, it should be emphasized that specific knowledge is required for the presented subjective methodology.

In strong field ionization of methyl iodide initiated by elliptically polarized few-cycle pulses, a significant correlation was observed between the carrier-envelope phases (CEPs) of the laser and the preferred ejection direction of methyl cation arising from dissociative double ionization. This was attributed to the carrier-envelope phase dependent double ionization yields of methyl iodide. This observation provides a new way for monitoring the absolute CEPs of few-cycle pulses by observing the ion momentum distributions.

We present two novel federated learning (FL) schemes that mitigate the effect of straggling devices by introducing redundancy on the devices’ data across the network. Compared to other schemes in the literature, which deal with stragglers or device dropouts by ignoring their contribution, the proposed schemes do not suffer from the client drift problem. The first scheme, CodedPaddedFL, mitigates the effect of stragglers while retaining the privacy level of conventional FL. It combines one-time padding for user data privacy with gradient codes to yield straggler resiliency. The second scheme, CodedSecAgg, provides straggler resiliency and robustness against model inversion attacks and is based on Shamir’s secret sharing. We apply CodedPaddedFL and CodedSecAgg to a classification problem. For a scenario with 120 devices, CodedPaddedFL achieves a speed-up factor of 18 for an accuracy of 95% on the MNIST dataset compared to conventional FL. Furthermore, it yields similar performance in terms of latency compared to a recently proposed scheme by Prakash et al. without the shortcoming of additional leakage of private data. CodedSecAgg outperforms the state-of-the-art secure aggregation scheme LightSecAgg by a speed-up factor of 6.6–18.7 for the MNIST dataset for an accuracy of 95%.

Glycol nucleic acid (GNA) is an acyclic nucleic acid analog connected via phosphodiester bonds. Crystal structures of RNA–GNA chimeric duplexes indicated that nucleotides of the right-handed (S)-GNA were better accommodated in the right-handed RNA duplex than were the left-handed (R)-isomers. GNA nucleotides adopt a rotated nucleobase orientation within all duplex contexts, pairing with complementary RNA in a reverse Watson–Crick mode, which explains the inabilities of GNA C and G to form strong base pairs with complementary nucleotides. Transposition of the hydrogen bond donor and acceptor pairs using novel (S)-GNA isocytidine and isoguanosine nucleotides resulted in stable base-pairing with the complementary G and C ribonucleotides, respectively. GNA nucleotide or dinucleotide incorporation into an oligonucleotide increased resistance against 3′-exonuclease-mediated degradation. Consistent with the structural observations, small interfering RNAs (siRNAs) modified with (S)-GNA had greater in vitro potencies than identical sequences containing (R)-GNA. (S)-GNA is well tolerated in the seed regions of antisense and sense strands of a GalNAc-conjugated siRNA in vitro. The siRNAs containing a GNA base pair in the seed region had in vivo potency when subcutaneously injected into mice. Importantly, seed pairing destabilization resulting from a single GNA nucleotide at position 7 of the antisense strand mitigated RNAi-mediated off-target effects in a rodent model. Two GNA-modified siRNAs have shown an improved safety profile in humans compared with their non-GNA-modified counterparts, and several additional siRNAs containing the GNA modification are currently in clinical development.

Low-voltage power fuses in new applications in dc networks are faced with changing requirements. Fast and reliable switching characteristics are needed, particularly to protect photovoltaic and battery storage systems. Due to the short fusing times in the event of short circuits, fuse elements made of silver are used. A tin solder is applied to the silver fuse element to protect the circuit from overcurrents. In the case of overcurrents in particular, the requirements for fuses in photovoltaic systems have changed compared to conventional semiconductor protection measures. For this reason, the fusing behavior at low overcurrents was investigated for silver fuse elements with tin solder. The diffusion from silver into liquid tin was analyzed during the fusing process. In the case of the latter, the influence of the temperature gradient along the solder was investigated as a design criterion in addition to the absolute temperature. A shorter fusing time with less scatter was found for specially adapted fuse elements with higher temperature gradients along the solder. The respective diffusion process could be analyzed based on microsections of the solder from interrupted fusing tests. For this purpose, energy-dispersive X-ray spectroscopy (EDX) measurements and threshold segmentations of the microsections were carried out. The temperature gradient along the solder initiated convective movements of silver atoms within the solder. More silver was dissolved in the liquid tin on the warmer side of the solder. Silver-rich particles precipitated on the cooler side of the solder and kept the concentration gradient up on the warmer side. The faster fusing process at higher temperature gradients could be correlated with an altered diffusion mechanism. With these investigations, a new and significant design parameter for fuse elements was determined. Silver fuse elements for protection of overcurrents in full-range fuses can now be easily adapted to new and future requirements.

The further evolution of product portfolios is driven by changes in the company's global and local environment. On the one hand, megatrends have a high and long-lasting influence on the evolution of product portfolios. For example, digitalization enables the networking of products. On the other hand, drastic market changes have an impact on the portfolio. These tend to occur suddenly and require a resilient attitude from manufacturing companies. These two forces affect each element of the product portfolio in the form of new customer needs, new technologies, legal requirements, and competitive pressures. As a result, product portfolios need to evolve constantly. Manufacturing companies already engage in this behavior, resulting in the establishment of heuristics from their experience. But there is no structured way to help manufacturing companies evolve their product portfolios. This paper deals with the characterization and structuring of interacting forces for a resilient, future-robust evolution of the product portfolio. First, the relevance of the problem is presented, then the knowledge base is identified, and finally, a model representation of reality is developed.

Impaired proinsulin-to-insulin processing in pancreatic β-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. 1,2), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. 3–8); nonetheless, the role of specific SL species in β-cell function and demise is unclear. Here we define the lipid signature of T2D-associated β-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. β-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL–protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum–Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in β-cell function and T2D-associated β-cell failure.

The needs of cyclists are becoming increasingly important in transportation planning. More and more bicycle simulators are being developed to study traffic behaviour and to test infrastructure measures in a cost-effective and safe way. However, in order to be able to transfer results from the simulation to reality, it must be ensured that the simulator reproduces a realistic traffic behaviour. Therefore, we conducted a study in which we compared the gaze behaviour within a simulator with a curved screen to the gaze behaviour in the field. Our results show that the gaze behaviour differs: in the simulator the gaze distribution is rather horizontal while in the field study it is vertical. In addition, more fixations respectively visits are performed in the field study. For most regions the average visit duration is significantly shorter in the field study. Therefore, the gaze behaviour was more active in the field study than in the simulation.