bluuebunny/crossref_metadata_2025 huggingface dataset:
Zahlungsbereitschaft für Insektizid-imprägnierte
Moskitonetze zur Malariaprophylaxe in Subsahara-Afrika – eine
systematische Literaturrecherche
Authors: Kemper Magdalena , Mahlich Jörg
Published: May 2023

Zielsetzung Studien zur Zahlungsbereitschaft von
Insektizid-imprägnierten Moskitonetzen zur Malariaphrophylaxe wurden
identifiziert und darauf aufbauend Maßnahmen zur Stimulierung der
Nachfrage abgeleitet.

Methodik Eine systematische Literaturrecherche wurde für den
Zeitraum 2012 bis 2022 und für die Region Subsahara-Afrika
durchgeführt.

Ergebnisse Acht relevante Veröffentlichungen wurden identifiziert.
Die Zahlungsbereitschaft für Insektizid-imprägnierte
Moskitonetze lag bei niedrigen Einkommensschichten in allen untersuchten Studien
deutlich unter dem Marktpreis. Der wahrgenommene Nutzen der Moskitonetze und das
allgemeine Wissen über Malaria und deren Prävention
erhöhen die Zahlungsbereitschaft.

Schlussfolgerungen Kurzfristig ist die kostenlose Verteilung für
Haushalte mit niedrigem Einkommen unumgänglich. Langfristig sollte der
Fokus auf gesundheitlicher Aufklärung liegen.
Bereavement Care – wie Pflegende trauernde Angehörige besser begleiten können
Authors: Kluger Lina , Krutter Simon
Published: May 2023

Intensivpflege orientiert sich an den individuellen Bedürfnissen der kritisch kranken Patientinnen und Patienten. Hinter jedem Patienten stehen jedoch meist auch nahe Angehörige, die ebenfalls in den Behandlungsplan miteinzubeziehen sind und deren Unterstützung zu den wesentlichen Aufgaben professionell Pflegender auf Intensivstationen gehört. Bei der Entscheidungsfindung am Lebensende beim Übergang von kurativer zu palliativer Therapie sind die Angehörigen die zentralen Ansprechpartner.
Verlaufsevaluation eines multimodalen Therapieprogrammes für
Methamphetamin-konsumierende Schwangere, Mütter und
Väter
Authors: Spreer Maik , Petzold Johannes , Krüger Maria , Weber Benjamin , Hahn Susanna , P. Pyrc Cornelia , S. Zimmermann Ulrich , Pilhatsch Maximilian
Published: May 2023

Ziel Verlaufsevaluation des suchttherapeutischen Teils des multimodalen
Therapieprogramms „Mama Denk an mich“, einer
interdisziplinären Zusammenarbeit mehrerer Kliniken des
Universitätsklinikums Dresden mit den örtlichen
Jugendämtern und Suchtberatungsstellen.

Methode Behandlungsverlaufs- und Stichprobenbeschreibung der ersten 100
Patienten mit einer metamphetaminbezogenen Störung und prospektive
Beobachtungsstudie der Therapieergebnisse.

Ergebnisse Neben einem hohen Anteil an Erstbehandelten (51%) und
einem jungen Durchschnittsalter (29 Jahre) fiel die Stichprobe durch
prekäre sozioökonomische Verhältnisse und zahlreiche
Komorbiditäten auf. Dennoch lässt die hohe Adhärenzrate
(68%) auf eine gute Wirksamkeit der verwendeten Therapiemethoden
schließen.

Schlussfolgerung Eltern- bzw. Schwangerschaft stellen eine Gelegenheit
dar, selbst schwere Fälle von Methamphetaminabhängigkeit mit
psychiatrischen Komorbiditäten für eine wirksame ambulante
Suchttherapie zu motivieren.
Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients
Authors: Nogueira Renata , Couto Christian Marques , Oliveira Pérola de , Martins Bernardo José Alves Ferreira , Montanaro Vinícius Viana Abreu
Published: May 2023

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil.

Methods We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation.

Results We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively.

Conclusion The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.
Liebe Leserinnen und Leser,
Authors: Bischoff Stephan C.
Published: May 2023

das zweite Heft des Jahres greift im Weiterbildungs-Artikel (cme) ein besonders
wichtiges Thema auf: „Adipositas und Krebs“ von den Kollegen und
Kolleginnen der Onkologie und Diabetologie der Universität Lübeck.
Die Autoren zeigen nicht nur, dass Adipositas mit einem erhöhten Krebsrisiko
assoziiert ist, sondern auch, dass sich Adipositas primär auf das
Krebserkrankungsrisiko und nicht auf die Überlebenswahrscheinlichkeit
auswirkt. Während die signifikante Gewichtsreduktion einen therapeutischen
Nutzen im Hinblick auf die Krebsinzidenz zu bringen scheint, müssen
pharmakologische Interventionen noch auf ihre diesbezügliche Eignung
evaluiert werden.
Riemann–Hilbert problem for the Fokas–Lenells equation in the presence of high-order discrete spectrum with non-vanishing boundary conditions
Authors: Zhang Xiao-Fan , Tian Shou-Fu
Published: May 2023

We extend the Riemann–Hilbert (RH) method to study the Fokas–Lenells (FL) equation with nonzero boundary conditions at infinity and successfully find its multiple soliton solutions with one high-order pole and N high-order poles. The mathematical structures of the FL equation are constructed, including global conservation laws and local conservation laws. Then, the conditions (analytic, symmetric, and asymptotic properties) needed to construct the RH problem are obtained by analyzing the spectral problem. The reflection coefficient r(z) with two cases appearing in the RH problem is considered, including one high-order pole and N high-order poles. In order to overcome the difficulty of establishing the residue expressions corresponding to high-order poles, we introduce the generalized residue formula. Finally, the expression of exact soliton solutions with reflectionless potential is further derived by a closed algebraic system.
High-performance p-channel CuIBr thin-film transistor synthesized from solution in the atmosphere
Authors: Wei Wei , Gao Ming , Wang Zhiyong , Zhang Yong-Wei , Yu Zhi Gen , Chim Wai Kin , Zhu Chunxiang
Published: May 2023

The p-type transparent semiconductor CuI has a high potential to be used in thin film transistors (TFTs) due to high hole mobility and solution processability. However, the lower copper vacancy formation energy and the subsequent high hole concentration in CuI lead to a low on/off current ratio (ION/IOFF) for CuI TFT devices. The density functional theory results suggest that the copper vacancy formation energy increases with the CuBr content in the Br-doped CuI film, resulting in lower hole concentration. Alloying CuI with CuBr is proposed to reduce the hole concentration in the CuIBr alloy. The CuIBr TFTs with Br content ranging from 0% to 10% were fabricated using the solution method. It is found that the hole mobility decreases from 8 to 1 cm2 V−1 s−1, while the ION/IOFF ratio increases from 102 to 104 with the increasing Br content. The CuIBr TFT with 7.5% Br content exhibits a high hole mobility larger than 5 cm2 V−1 s−1 and high ION/IOFF ratio of 104, which paves the way for inorganic-based CMOS circuits on flexible and transparent substrates.
The role of biomechanical factors in models of intervertebral disc degeneration across multiple length scales
Authors: Lazaro-Pacheco Daniela , Mohseni Mina , Rudd Samuel , Cooper-White Justin , Holsgrove Timothy Patrick
Published: May 2023

Low back pain is the leading cause of disability, producing a substantial socio-economic burden on healthcare systems worldwide. Intervertebral disc (IVD) degeneration is a primary cause of lower back pain, and while regenerative therapies aimed at full functional recovery of the disc have been developed in recent years, no commercially available, approved devices or therapies for the regeneration of the IVD currently exist. In the development of these new approaches, numerous models for mechanical stimulation and preclinical assessment, including in vitro cell studies using microfluidics, ex vivo organ studies coupled with bioreactors and mechanical testing rigs, and in vivo testing in a variety of large and small animals, have emerged. These approaches have provided different capabilities, certainly improving the preclinical evaluation of these regenerative therapies, but challenges within the research environment, and compromises relating to non-representative mechanical stimulation and unrealistic test conditions, remain to be resolved. In this review, insights into the ideal characteristics of a disc model for the testing of IVD regenerative approaches are first assessed. Key learnings from in vivo, ex vivo, and in vitro IVD models under mechanical loading stimulation to date are presented alongside the merits and limitations of each model based on the physiological resemblance to the human IVD environment (biological and mechanical) as well as the possible feedback and output measurements for each approach. When moving from simplified in vitro models to ex vivo and in vivo approaches, the complexity increases resulting in less controllable models but providing a better representation of the physiological environment. Although cost, time, and ethical constraints are dependent on each approach, they escalate with the model complexity. These constraints are discussed and weighted as part of the characteristics of each model.
Effective local potentials for density and density-matrix functional approximations with non-negative screening density
Authors: Pitts Thomas C. , Bousiadi Sofia , Gidopoulos Nikitas I. , Lathiotakis Nektarios N.
Published: May 2023

A way to improve the accuracy of the spectral properties in density functional theory (DFT) is to impose constraints on the effective, Kohn–Sham (KS), local potential [J. Chem. Phys. 136, 224109 (2012)]. As illustrated, a convenient variational quantity in that approach is the “screening” or “electron repulsion” density, ρrep, corresponding to the local, KS Hartree, exchange and correlation potential through Poisson’s equation. Two constraints, applied to this minimization, largely remove self-interaction errors from the effective potential: (i) ρrep integrates to N − 1, where N is the number of electrons, and (ii) ρrep ≥ 0 everywhere. In this work, we introduce an effective “screening” amplitude, f, as the variational quantity, with the screening density being ρrep = f2. In this way, the positivity condition for ρrep is automatically satisfied, and the minimization problem becomes more efficient and robust. We apply this technique to molecular calculations, employing several approximations in DFT and in reduced density matrix functional theory. We find that the proposed development is an accurate, yet robust, variant of the constrained effective potential method.
Structural properties of MBE-grown CdTe (133)B buffer layers on GaAs (211)B substrates with CdZnTe/CdTe superlattice-based dislocation filtering layers
Authors: Pan Wenwu , Ma Shuo , Sun Xiao , Nath Shimul Kanti , Zhang Songqing , Gu Renjie , Zhang Zekai , Faraone Lorenzo , Lei Wen
Published: May 2023

The ever-present demand for high-performance HgCdTe infrared detectors with larger array size and lower cost than currently available technologies based on lattice-matched CdZnTe (211)B substrates has fuelled research into heteroepitaxial growth of HgCdTe and CdTe buffer layers on lattice-mismatched alternative substrates with a (211)B orientation. Driven by the large lattice mismatch, the heteroepitaxial growth of (Hg)CdTe can result in (133)B-orientated material, which, however, has been less explored in comparison to (211)B-oriented growth. Herein, we report on the structural properties of heteroepitaxially grown single-crystal II–VI CdTe (133)B-oriented buffer layers on III–V GaAs (211)B substrates. Azimuthal-dependent x-ray double-crystal rocking curve measurements for the CdTe buffer layers show that the full-width at half-maximum value obtained along the GaAs [1¯11] direction is narrower than that obtained along the GaAs [011¯] direction, which is presumably related to the in-plane anisotropic structural characteristics of the grown CdTe layers. By incorporating strained CdZnTe/CdTe superlattice-based dislocation filtering layers (DFLs), a significant improvement in material quality has been achieved in (133)B-orientated CdTe buffer layers, including a reduced etch pit density in the low-105 cm−2 range and improved surface roughness. These results indicate that the CdTe (133)B DFL buffer layer process is a feasible approach for growing high-quality CdTe and HgCdTe materials on large-area, low-cost alternative substrates.
In situ measurements of non-equilibrium positron state defects during He irradiation in Si
Authors: Auguste R. , Liedke M. O. , Butterling M. , Uberuaga B. P. , Selim F. A. , Wagner A. , Hosemann P.
Published: May 2023

Radiation-induced property changes in materials originate from the energy transfer from an incoming particle to the existing lattice, displacing atoms. The displaced atoms can cause the formation of extended defects including dislocation loops, voids, or precipitates. The non-equilibrium defects created during damage events determine the extent of these larger defects and are a function of dose rate, material, and temperature. However, these defects are transient and can only be probed indirectly. This work presents direct experimental measurements and evidence of irradiated non-equilibrium vacancy formation, where in situ positron annihilation spectroscopy was used to prove the generation of non-equilibrium defects in silicon.
Giant and broadband THz and IR emission in drift-biased graphene-based hyperbolic nanostructures
Authors: Wang L. , Paul N. K. , Hihath J. , Gomez-Diaz J. S.
Published: May 2023

We demonstrate that Cherenkov radiation can be manipulated in terms of operation frequency, bandwidth, and efficiency by simultaneously controlling the properties of drifting electrons and the photonic states supported by their surrounding media. We analytically show that the radiation rate strongly depends on the momentum of the excited photonic state, in terms of magnitude, frequency dispersion, and its variation vs the properties of the drifting carriers. This approach is applied to design and realize miniaturized, broadband, tunable, and efficient terahertz and far-infrared sources by manipulating and boosting the coupling between drifting electrons and engineered hyperbolic modes in graphene-based nanostructures. The broadband, dispersive, and confined nature of hyperbolic modes relax momentum matching issues, avoid using electron beams, and drastically enhance the radiation rate—allowing that over 90% of drifting electrons emit photons. Our findings open an exciting paradigm for the development of solid-state terahertz and infrared sources.
On the statistical evaluation of bubbly flows using Voronoi cells grouped in clusters with fixed cell count
Authors: Weber L. , Gabriel S. , Class A. G.
Published: May 2023

The extraction of statistical information from bubbly flow experiments is crucial for numerical studies. Knowledge regarding probability distributions is particularly relevant in cases where a model relying solely on the use of mean values would lead to inaccurate results. As such, existing studies have focused on evaluating spatial distributions and local histograms for the void fraction, bubble density, and bubble size. However, the traditional box-counting method, employed by various studies, results in inconsistencies when deriving these quantities, especially when the respective two-phase flow features regions with low bubble densities or density gradients. This study demonstrates the application and benefits of combining Voronoi diagrams with a constrained K-Means clustering algorithm as a method for analyzing bubbly flows. We conduct three test cases: The first two cases use synthetic snapshots with prescribed characteristics to show the influence of evaluation settings and to critically quantify the errors, and the last test uses snapshot data of a plunging-jet experiment with air entrainment. We, then, compare the identified entrainment rate and the mean void-fraction distribution with empirical values from the literature. All three test cases show good agreement with the prescribed field characteristics (synthetic snapshots) and the data from the literature (experiment). Beyond demonstrating its applicability, we also show how this method can derive local histograms more consistently. The derivation is robust throughout the domain in comparison with traditional methods. For these reasons, we conclude that this method provides good estimates of spatial distributions.
Universal behavior in complex-mediated reactions: Dynamics of S(1D) + o-D2 → D + SD at low collision energies
Authors: Lara Manuel , Jambrina P. G. , Aoiz F. J.
Published: May 2023

Reactive and elastic cross sections and rate coefficients have been calculated for the S(1D) + D2(v = 0, j = 0) reaction using a modified hyperspherical quantum reactive scattering method. The considered collision energy ranges from the ultracold regime, where only one partial wave is open, up to the Langevin regime, where many of them contribute. This work presents the extension of the quantum calculations, which in a previous study were compared with the experimental results, down to energies in the cold and ultracold domains. Results are analyzed and compared with the universal case of the quantum defect theory by Jachymski et al. [Phys. Rev. Lett. 110, 213202 (2013)]. State-to-state integral and differential cross sections are also shown covering the ranges of low-thermal, cold, and ultracold collision energy regimes. It is found that at E/kB < 1 K, there are substantial departures from the expected statistical behavior and that dynamical features become increasingly important with decreasing collision energy, leading to vibrational excitation.
Origins of epitaxial macro-terraces and macro-steps on GaN substrates
Authors: Liao Michael E. , Olsen William L. , Huynh Kenny , Luccioni Dorian P. , Wang Yekan , Huang XianRong , Wojcik Michael J. , Allerman Andrew A. , Goorsky Mark S.
Published: May 2023

Localized lattice distortions in GaN substrates can serve as nucleation sites for epitaxial macro-steps and macro-terraces. These detrimental macro-scale features give rise to optically hazy homoepitaxial GaN surfaces. After nucleating, these macro-features grow laterally along the surface and coalesce, leading to significant coverage of the wafer surface. Dot-core GaN substrates consisting of a periodic array of cores were used as a defect-engineered system, where dislocations are intentionally concentrated at the cores. The high density of threading dislocations at the cores induced localized lattice distortions. These distortions are associated predominantly with lattice tilt on the order of hundreds of arcsec across ∼0.5 mm laterally along the wafer surface. The resulting macro-features that nucleated at these localized distorted sites were made up of macro-terraces with lengths ranging ∼30–∼150 μm and macro-step heights ranging ∼200–∼400 nm. Another source of localized distortion was threading screw dislocations or GaN nanopipes that resulted in spiral growth and hillock formation. Based on x-ray topography and optical microscopy measurements, we speculate that the coalescence of hillocks evolves into macro-terraces and macro-steps. While previous studies focused on the substrate miscut as a means to control macro-feature formation, we show that localized lattice tilt from defects is another important contributor to macro-feature formation.
Plasma-enhanced atomic layer deposited SiO2 enables positive thin film charge and surface recombination velocity of 1.3 cm/s on germanium
Authors: Liu Hanchen , Pasanen Toni P. , Leiviskä Oskari , Isometsä Joonas , Fung Tsun Hang , Yli-Koski Marko , Miettinen Mikko , Laukkanen Pekka , Vähänissi Ville , Savin Hele
Published: May 2023

The excellent field-effect passivation provided by aluminum oxide (Al2O3) on germanium surfaces relies on the high negative fixed charge present in the film. However, in many applications, a neutral or a positive charge would be preferred. Here, we investigate the surface passivation performance and the charge polarity of plasma-enhanced atomic layer deposited (PEALD) silicon oxide (SiO2) on Ge. The results show that even a 3 nm thick PEALD SiO2 provides a positive charge density (Qtot, ∼2.6 × 1011 cm−2) and a relatively good surface passivation (maximum surface recombination velocity SRVmax ∼16 cm/s). When the SiO2 thin film is capped with an ALD Al2O3 layer, the surface passivation improves further and a low midgap interface defect density (Dit) of ∼1 × 1011 eV−1 cm−2 is achieved. By varying the SiO2 thickness under the Al2O3 capping, it is possible to control the Qtot from virtually neutral (∼2.8 × 1010 cm−2) to moderately positive (∼8.5 × 1011 cm−2) values. Consequently, an excellent SRVmax as low as 1.3 cm/s is obtained using optimized SiO2/Al2O3 layer thicknesses. Finally, the origin of the positive charge as well as the interface defects related to PEALD SiO2 are discussed.
Rapid monitoring of ecological persistence
Authors: Song Chuliang , Simmons Benno I. , Fortin Marie-Josée , Gonzalez Andrew , Kaiser-Bunbury Christopher N. , Saavedra Serguei
Published: May 2023

Effective conservation of ecological communities requires accurate and up-to-date information about whether species are persisting or declining to extinction. The persistence of an ecological community is supported by its underlying network of species interactions. While the persistence of the network supporting the whole community is the most relevant scale for conservation, in practice, only small subsets of these networks can be monitored. There is therefore an urgent need to establish links between the small snapshots of data conservationists can collect, and the “big picture” conclusions about ecosystem health demanded by policymakers, scientists, and societies. Here, we show that the persistence of small subnetworks (motifs) in isolation—that is, their persistence when considered separately from the larger network of which they are a part—is a reliable probabilistic indicator of the persistence of the network as a whole. Our methods show that it is easier to detect if an ecological community is not persistent than if it is persistent, allowing for rapid detection of extinction risk in endangered systems. Our results also justify the common practice of predicting ecological persistence from incomplete surveys by simulating the population dynamics of sampled subnetworks. Empirically, we show that our theoretical predictions are supported by data on invaded networks in restored and unrestored areas, even in the presence of environmental variability. Our work suggests that coordinated action to aggregate information from incomplete sampling can provide a means to rapidly assess the persistence of entire ecological networks and the expected success of restoration strategies.
The PLOD2/succinate axis regulates the epithelial–mesenchymal plasticity and cancer cell stemness
Authors: Tong Yuxin , Qi Yifei , Xiong Gaofeng , Li Junyan , Scott Timothy L. , Chen Jie , He Daheng , Li Linzhang , Wang Chi , Lane Andrew N. , Xu Ren
Published: May 2023

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with elevation of cytoplasmic succinate during the EMT process. Silencing of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.
Evolutionary dynamics within and among competing groups
Authors: Cooney Daniel B. , Levin Simon A. , Mori Yoichiro , Plotkin Joshua B.
Published: May 2023

Biological and social systems are structured at multiple scales, and the incentives of individuals who interact in a group may diverge from the collective incentive of the group as a whole. Mechanisms to resolve this tension are responsible for profound transitions in evolutionary history, including the origin of cellular life, multicellular life, and even societies. Here, we synthesize a growing literature that extends evolutionary game theory to describe multilevel evolutionary dynamics, using nested birth–death processes and partial differential equations to model natural selection acting on competition within and among groups of individuals. We analyze how mechanisms known to promote cooperation within a single group—including assortment, reciprocity, and population structure—alter evolutionary outcomes in the presence of competition among groups. We find that population structures most conducive to cooperation in multiscale systems can differ from those most conducive within a single group. Likewise, for competitive interactions with a continuous range of strategies we find that among-group selection may fail to produce socially optimal outcomes, but it can nonetheless produce second-best solutions that balance individual incentives to defect with the collective incentives for cooperation. We conclude by describing the broad applicability of multiscale evolutionary models to problems ranging from the production of diffusible metabolites in microbes to the management of common-pool resources in human societies.
G-quadruplexes rescuing protein folding
Authors: Son Ahyun , Huizar Cabral Veronica , Huang Zijue , Litberg Theodore J. , Horowitz Scott
Published: May 2023

Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of
Escherichia coli
. However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in
E. coli
further demonstrate that these G4s primarily improve protein folding quality in
E. coli
as opposed to preventing protein aggregation. The ability of a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins.
Structure of WNT inhibitor adenomatosis polyposis coli down-regulated 1 (APCDD1), a cell-surface lipid-binding protein
Authors: Hsieh Fu-Lien , Chang Tao-Hsin , Gabelli Sandra B. , Nathans Jeremy
Published: May 2023

Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues,
APCDD1
transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed β-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.
Microsaccades are directed toward the midpoint between targets in a variably cued attention task
Authors: Willett Shawn M. , Mayo J. Patrick
Published: May 2023

Reliable, noninvasive biomarkers that reveal the internal state of a subject are an invaluable tool for neurological diagnoses. Small fixational eye movements, called microsaccades, are a candidate biomarker thought to reflect a subject's focus of attention [Z. M. Hafed, J. J. Clark,VisionRes.42, 2533–2545 (2002); R. Engbert, R. Kliegl,VisionRes.43, 1035–1045 (2003)]. The linkage between the direction of microsaccades and attention has mainly been demonstrated using explicit and unambiguous attentional cues. However, the natural world is seldom predictable and rarely provides unambiguous information. Thus, a useful biomarker must be robust to such changes in environmental statistics. To determine how well microsaccades reveal visual-spatial attention across behavioral contexts, we analyzed these fixational eye movements in monkeys performing a conventional change detection task. The task included two stimulus locations and variable cue validities across blocks of trials. Subjects were adept at the task, showing precise and graded modulations of visual attention for subtle target changes and performing better and faster when the cue was more reliable [J. P. Mayo, J. H. R. Maunsell,J. Neurosci. 36, 5353 (2016)]. However, over tens of thousands of microsaccades, we found no difference in microsaccade direction between cued locations when cue variability was high nor between hit and miss trials. Instead, microsaccades were made toward the midpoint of the two target locations, not toward individual targets. Our results suggest that the direction of microsaccades should be interpreted with caution and may not be a reliable measure of covert spatial attention in more complex viewing conditions.
Antenna-coupled infrared nanospectroscopy of intramolecular vibrational interaction
Authors: Wilcken Roland , Nishida Jun , Triana Johan F. , John-Herpin Aurelian , Altug Hatice , Sharma Sandeep , Herrera Felipe , Raschke Markus B.
Published: May 2023

Many photonic and electronic molecular properties, as well as chemical and biochemical reactivities are controlled by fast intramolecular vibrational energy redistribution (IVR). This fundamental ultrafast process limits coherence time in applications from photochemistry to single quantum level control. While time-resolved multidimensional IR-spectroscopy can resolve the underlying vibrational interaction dynamics, as a nonlinear optical technique it has been challenging to extend its sensitivity to probe small molecular ensembles, achieve nanoscale spatial resolution, and control intramolecular dynamics. Here, we demonstrate a concept how mode-selective coupling of vibrational resonances to IR nanoantennas can reveal intramolecular vibrational energy transfer. In time-resolved infrared vibrational nanospectroscopy, we measure the Purcell-enhanced decrease of vibrational lifetimes of molecular vibrations while tuning the IR nanoantenna across coupled vibrations. At the example of a Re-carbonyl complex monolayer, we derive an IVR rate of (25
±
8) cm
−1
corresponding to (450
±
150) fs, as is typical for the fast initial equilibration between symmetric and antisymmetric carbonyl vibrations. We model the enhancement of the cross-vibrational relaxation based on intrinsic intramolecular coupling and extrinsic antenna-enhanced vibrational energy relaxation. The model further suggests an anti-Purcell effect based on antenna and laser–field–driven vibrational mode interference which can counteract IVR-induced relaxation. Nanooptical spectroscopy of antenna-coupled vibrational dynamics thus provides for an approach to probe intramolecular vibrational dynamics with a perspective for vibrational coherent control of small molecular ensembles.
Melt rates in the kilometer-size grounding zone of Petermann Glacier, Greenland, before and during a retreat
Authors: Ciracì Enrico , Rignot Eric , Scheuchl Bernd , Tolpekin Valentyn , Wollersheim Michael , An Lu , Milillo Pietro , Bueso-Bello Jose-Luis , Rizzoli Paola , Dini Luigi
Published: May 2023

Warming of the ocean waters surrounding Greenland plays a major role in driving glacier retreat and the contribution of glaciers to sea level rise. The melt rate at the junction of the ocean with grounded ice—or grounding line—is, however, not well known. Here, we employ a time series of satellite radar interferometry data from the German TanDEM-X mission, the Italian COSMO-SkyMed constellation, and the Finnish ICEYE constellation to document the grounding line migration and basal melt rates of Petermann Glacier, a major marine-based glacier of Northwest Greenland. We find that the grounding line migrates at tidal frequencies over a kilometer-wide (2 to 6 km) grounding zone, which is one order of magnitude larger than expected for grounding lines on a rigid bed. The highest ice shelf melt rates are recorded within the grounding zone with values from 60 ± 13 to 80 ± 15 m/y along laterally confined channels. As the grounding line retreated by 3.8 km in 2016 to 2022, it carved a cavity about 204 m in height where melt rates increased from 40 ± 11 m/y in 2016 to 2019 to 60 ± 15 m/y in 2020 to 2021. In 2022, the cavity remained open during the entire tidal cycle. Such high melt rates concentrated in kilometer-wide grounding zones contrast with the traditional plume model of grounding line melt which predicts zero melt. High rates of simulated basal melting in grounded glacier ice in numerical models will increase the glacier sensitivity to ocean warming and potentially double projections of sea level rise.
Mutation enhances cooperation in direct reciprocity
Authors: Tkadlec Josef , Hilbe Christian , Nowak Martin A.
Published: May 2023

Direct reciprocity is a powerful mechanism for the evolution of cooperation based on repeated interactions between the same individuals. But high levels of cooperation evolve only if the benefit-to-cost ratio exceeds a certain threshold that depends on memory length. For the best-explored case of one-round memory, that threshold is two. Here, we report that intermediate mutation rates lead to high levels of cooperation, even if the benefit-to-cost ratio is only marginally above one, and even if individuals only use a minimum of past information. This surprising observation is caused by two effects. First, mutation generates diversity which undermines the evolutionary stability of defectors. Second, mutation leads to diverse communities of cooperators that are more resilient than homogeneous ones. This finding is relevant because many real-world opportunities for cooperation have small benefit-to-cost ratios, which are between one and two, and we describe how direct reciprocity can attain cooperation in such settings. Our result can be interpreted as showing that diversity, rather than uniformity, promotes evolution of cooperation.
Complement contributes to antibody-mediated protection against repeated SHIV challenge
Authors: Goldberg Benjamin S. , Spencer David A. , Pandey Shilpi , Ordonez Tracy , Barnette Philip , Yu Yun , Gao Lina , Dufloo Jérémy , Bruel Timothée , Schwartz Olivier , Ackerman Margaret E. , Hessell Ann J.
Published: May 2023

The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization breadth and potency, it remains unclear whether augmenting the effector functions elicited by broadly neutralizing antibodies (bNAbs) may also improve their clinical potential. Among these effector functions, complement-mediated activities, which can culminate in the lysis of virions or infected cells, have been the least well studied. Here, functionally modified variants of the second-generation bNAb 10-1074 with ablated and enhanced complement activation profiles were used to examine the role of complement-associated effector functions. When administered prophylactically against simian-HIV challenge in rhesus macaques, more bNAb was required to prevent plasma viremia when complement activity was eliminated. Conversely, less bNAb was required to protect animals from plasma viremia when complement activity was enhanced. These results suggest that complement-mediated effector functions contribute to in vivo antiviral activity, and that their engineering may contribute to the further improvements in the efficacy of antibody-mediated prevention strategies.
Polymer folding through active processes recreates features of genome organization
Authors: Goychuk Andriy , Kannan Deepti , Chakraborty Arup K. , Kardar Mehran
Published: May 2023

From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, active processes. Signatures of activity have been measured in the context of chromatin motion, which shows spatial correlations and enhanced subdiffusion only in the presence of adenosine triphosphate. Moreover, chromatin motion varies with genomic coordinate, pointing toward a heterogeneous pattern of active processes along the sequence. How do such patterns of activity affect the conformation of a polymer such as chromatin? We address this question by combining analytical theory and simulations to study a polymer subjected to sequence-dependent correlated active forces. Our analysis shows that a local increase in activity (larger active forces) can cause the polymer backbone to bend and expand, while less active segments straighten out and condense. Our simulations further predict that modest activity differences can drive compartmentalization of the polymer consistent with the patterns observed in chromosome conformation capture experiments. Moreover, segments of the polymer that show correlated active (sub)diffusion attract each other through effective long-ranged harmonic interactions, whereas anticorrelations lead to effective repulsions. Thus, our theory offers nonequilibrium mechanisms for forming genomic compartments, which cannot be distinguished from affinity-based folding using structural data alone. As a first step toward exploring whether active mechanisms contribute to shaping genome conformations, we discuss a data-driven approach.
S-lactoyl modification of KEAP1 by a reactive glycolytic metabolite activates NRF2 signaling
Authors: Ko Yeonjin , Hong Mannkyu , Lee Seungbeom , Kumar Manoj , Ibrahim Lara , Nutsch Kayla , Stanton Caroline , Sondermann Phillip , Sandoval Braddock , Bulos Maya L. , Iaconelli Jonathan , Chatterjee Arnab K. , Wiseman R. Luke , Schultz Peter G. , Bollong Michael J.
Published: May 2023

KEAP1 (Kelch-like ECH-associated protein), a cytoplasmic repressor of the oxidative stress responsive transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), senses the presence of electrophilic agents by modification of its sensor cysteine residues. In addition to xenobiotics, several reactive metabolites have been shown to covalently modify key cysteines on KEAP1, although the full repertoire of these molecules and their respective modifications remain undefined. Here, we report the discovery of sAKZ692, a small molecule identified by high-throughput screening that stimulates NRF2 transcriptional activity in cells by inhibiting the glycolytic enzyme pyruvate kinase. sAKZ692 treatment promotes the buildup of glyceraldehyde 3-phosphate, a metabolite which leads to S-lactate modification of cysteine sensor residues of KEAP1, resulting in NRF2-dependent transcription. This work identifies a posttranslational modification of cysteine derived from a reactive central carbon metabolite and helps further define the complex relationship between metabolism and the oxidative stress-sensing machinery of the cell.
Reconfigurable refraction manipulation at synthetic temporal interfaces with scalar and vector gauge potentials
Authors: Ye Han , Qin Chengzhi , Wang Shulin , Zhao Lange , Liu Weiwei , Wang Bing , Longhi Stefano , Lu Peixiang
Published: May 2023

Photonic gauge potentials, including scalar and vector ones, play fundamental roles in emulating photonic topological effects and for enabling intriguing light transport dynamics. While previous studies mainly focus on manipulating light propagation in uniformly distributed gauge potentials, here we create a series of gauge-potential interfaces with different orientations in a nonuniform discrete-time quantum walk and demonstrate various reconfigurable temporal-refraction effects. We show that for a lattice-site interface with the potential step along the lattice direction, the scalar potentials can yield total internal reflection (TIR) or Klein tunneling, while vector potentials manifest direction-invariant refractions. We also reveal the existence of penetration depth for the temporal TIR by demonstrating frustrated TIR with a double lattice-site interface structure. By contrast, for an interface emerging in the time-evolution direction, the scalar potentials have no effect on the packet propagation, while the vector potentials can enable birefringence, through which we further create a “temporal superlens” to achieve time-reversal operations. Finally, we experimentally demonstrate electric and magnetic Aharonov–Bohm effects using combined lattice-site and evolution-step interfaces of either scalar or vector potential. Our work initiates the creation of artificial heterointerfaces in synthetic time dimension by employing nonuniformly and reconfigurable distributed gauge potentials. This paradigm may find applications in optical pulse reshaping, fiber-optic communications, and quantum simulations.
Structure of the metazoan Rab7 GEF complex Mon1–Ccz1–Bulli
Authors: Herrmann Eric , Schäfer Jan-Hannes , Wilmes Stephan , Ungermann Christian , Moeller Arne , Kümmel Daniel
Published: May 2023

The endosomal system of eukaryotic cells represents a central sorting and recycling compartment linked to metabolic signaling and the regulation of cell growth. Tightly controlled activation of Rab GTPases is required to establish the different domains of endosomes and lysosomes. In metazoans, Rab7 controls endosomal maturation, autophagy, and lysosomal function. It is activated by the guanine nucleotide exchange factor (GEF) complex Mon1–Ccz1–Bulli (MCBulli) of the tri-longin domain (TLD) family. While the Mon1 and Ccz1 subunits have been shown to constitute the active site of the complex, the role of Bulli remains elusive. We here present the cryo-electron microscopy (cryo-EM) structure of MCBulli at 3.2 Å resolution. Bulli associates as a leg-like extension at the periphery of the Mon1 and Ccz1 heterodimers, consistent with earlier reports that Bulli does not impact the activity of the complex or the interactions with recruiter and substrate GTPases. While MCBulli shows structural homology to the related ciliogenesis and planar cell polarity effector (Fuzzy–Inturned–Wdpcp) complex, the interaction of the TLD core subunits Mon1-Ccz1 and Fuzzy–Inturned with Bulli and Wdpcp, respectively, is remarkably different. The variations in the overall architecture suggest divergent functions of the Bulli and Wdpcp subunits. Based on our structural analysis, Bulli likely serves as a recruitment platform for additional regulators of endolysosomal trafficking to sites of Rab7 activation.
Distinguishing homogeneous advanced oxidation processes in bulk water from heterogeneous surface reactions in organic oxidation
Authors: Zhang Ying-Jie , Chen Jie-Jie , Huang Gui-Xiang , Li Wen-Wei , Yu Han-Qing , Elimelech Menachem
Published: May 2023

Clarifying the reaction pathways at the solid–water interface and in bulk water solution is of great significance for the design of heterogeneous catalysts for selective oxidation of organic pollutants. However, achieving this goal is daunting because of the intricate interfacial reactions at the catalyst surface. Herein, we unravel the origin of the organic oxidation reactions with metal oxide catalysts, revealing that the radical-based advanced oxidation processes (AOPs) prevail in bulk water but not on the solid catalyst surfaces. We show that such differing reaction pathways widely exist in various chemical oxidation (e.g., high-valent Mn3+and MnOX) and Fenton and Fenton-like catalytic oxidation (e.g., Fe2+and FeOCl catalyzing H2O2, Co2+and Co3O4catalyzing persulfate) systems. Compared with the radical-based degradation and polymerization pathways of one-electron indirect AOP in homogeneous reactions, the heterogeneous catalysts provide unique surface properties to trigger surface-dependent coupling and polymerization pathways of a two-electron direct oxidative transfer process. These findings provide a fundamental understanding of catalytic organic oxidation processes at the solid–water interface, which could guide the design of heterogeneous nanocatalysts.
An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation
Authors: Kim Yeon Sun , Yuan Jia , Dewar Amanda , Borg Jean-Paul , Threadgill David W. , Sun Xiaofei , Dey Sudhansu K.
Published: May 2023

Implantation is the first direct encounter between the embryo and uterus during pregnancy, and
Hbegf
is the earliest known molecular signaling for embryo–uterine crosstalk during implantation. The downstream effectors of heparin-binding EGF (HB-EGF) in implantation remain elusive due to the complexity of EGF receptor family. This study shows that the formation of implantation chamber (crypt) triggered by HB-EGF is disrupted by uterine deletion of
Vangl2,
a key planar cell polarity component (PCP). We found that HB-EGF binds to ERBB2 and ERBB3 to recruit VANGL2 for tyrosine phosphorylation. Using in vivo models, we show that uterine VAGL2 tyrosine phosphorylation is suppressed in
Erbb2/Erbb3
double conditional knockout mice. In this context, severe implantation defects in these mice lend support to the critical role of HB-EGF-ERBB2/3-VANGL2 in establishing a two-way dialogue between the blastocyst and uterus. In addition, the result addresses an outstanding question how VANGL2 is activated during implantation. Taken together, these observations reveal that HB-EGF regulates the implantation process by influencing uterine epithelial cell polarity comprising VANGL2.