bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of intermodulation in a loaded-line phase shifter based on a polynomial varactor model
Authors: Mattsson Martin , Buisman Koen , Kuylenstierna Dan
Published: November 2024

This paper investigates if there is an optimum design of loaded-line phase shifters with respect to phase shift/loss figure of merit (FOM) and linearity. The investigation was performed by comparing six loaded-line phase shifters that were implemented in printed circuit board (PCB)technology with shunt-loaded hyperabrupt varactor-diodes. It was demonstrated that the hyperabrupt varactor’s C-V characteristics must be modeled with high accuracy to predict the nonlinear behavior. A polynomial varactor model was employed and experimentally validated. To extend the range of investigated parameter values, the extracted model was scaled and evaluated further in a circuit simulator. The investigation reveals that for a given varactor-capacitance, the phase shift/loss FOM is improved if the varactor-capacitance is evenly distributed and the unit cell length is much shorter than a quarter wavelength. The study demonstrates that the phase shift/loss depends mainly on the distribution of varactor-capacitance and Q factor. The intermodulation (IM) distortion is primarily proportional to the total varactor-capacitance per unit cell. The study also revealed that an increase in the varactor’s Q factor results in higher IM. Therefore, it is a trade-off between low loss and low IM.
Improving cole crop safety and weed control response with chloroacetamide and oxyfluorfen herbicide combinations
Authors: Sosnoskie Lynn M. , Besançon Thierry E.
Published: November 2024

In 2022, trials were carried out in New Jersey and New York to assess the efficacy of weed management and the response of two cole crops to various herbicide combinations and rates. The experiments involved the application of S-metolachlor and microencapsulated (ME) acetochlor either alone or combined with oxyfluorfen. Different application timings of oxyfluorfen were tested in greenhouse and field studies. Results from the greenhouse trials show that substituting S–metolachlor with ME acetochlor in over-the-top applied mixes with oxyfluorfen caused 15% to 22% less crop injury and increased seedling biomass by 33%. In field studies, nontreated plots exhibited significant weed growth, reaching up to 71% coverage 28 d after transplanting (DATr), whereas herbicide-treated plots exhibited weed cover at or below 10% by 28 DATr. Mixtures or sequential applications of oxyfluorfen and chloroacetamides achieved excellent control (≥99%) of the weed species complex compared to single applications of oxyfluorfen or chloroacetamides. However, applying both oxyfluorfen and a chloroacetamide posttransplanting, either as a tank mixture or in sequence, resulted in ≥19% injury. Despite the effective weed control achieved with herbicide treatments, mixing herbicides posttransplanting reduced relative commercial yield by 46% to 94% compared to oxyfluorfen applied alone or followed by chloroacetamides. The findings from these experiments will inform regional crop safety guidelines and support potential modifications to oxyfluorfen labels regarding sequential applications with chloroacetamides.
Italian Ryegrass Control Using a Capsule Suspension Formulation of S-metolachlor in Fenclorim-treated wheat
Authors: Norsworthy Jason K. , Noe Samuel C. , Avent Tristen H. , Butts Thomas R. , Roberts Trent L.
Published: November 2024

Italian ryegrass control is one of the most significant limitations in wheat production in the United States today. Resistance to Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA) Groups 1, 2, and 9 in Arkansas have further complicated postemergence control, whereas residual herbicides still show effective weed control. One problem is the potential of HRAC/WSSA Group 15 herbicides to injure wheat when applied preemergence, indicating the need for a herbicide safener. A series of experiments were conducted in Fayetteville, AR, to evaluate crop tolerance and Italian ryegrass control using a capsule suspension (CS) formulation of S-metolachlor in conjunction with fenclorim-treated wheat. Experiments were conducted as a two-factor factorial with S-metolachlor applied at three rates (0.37, 0.74, and 1.12 kg ai ha–1) and a microencapsulated formulation of acetochlor at 1.05 kg ai ha–1, and three rates of a fenclorim seed treatment at 0, 0.5, and 2.0 g ai kg–1 of seed. Separate experiments utilized either a preemergence (PRE) or a delayed-preemergence (DPRE) application timing. In both experiments, S-metolachlor at 0.74 and 1.12 kg ai ha–1 provided 77% to 96% control of Italian ryegrass by preharvest, whereas acetochlor only provided 49% to 72% control. Visible wheat injury from PRE applications ranged from 7% to 49% for all treatments 21 d after treatment (DAT), with a reduction in injury when fenclorim-treated wheat was used for both the 0.74 and 1.12 kg ai ha–1 rate of S-metolachlor. In the DPRE experiments, wheat injury ranged from 5% to 16% 21 DAT with no noticeable safening from the presence of fenclorim at any herbicide rate. The results of these experiments indicate that a DPRE application using a CS formulation of S-metolachlor would be more favorable for producers to mitigate the potential for injury to wheat while providing Italian ryegrass control. Additionally, at the DPRE application timing, fenclorim is unnecessary for S-metolachlor to be safely applied at the rates evaluated.
Complementary activity of trifludimoxazin and saflufenacil when used in combination for postemergence and residual weed control
Authors: Parra Rapado Liliana , Kölpin Frederik Uwe Gerhard , Zeyer Silke , Anders Ulrike , Piccard Laurent , Porri Aimone , Asher Scott
Published: November 2024

Trifludimoxazin is a new herbicide that inhibits protoporphyrinogen oxidase (PPO) and is targeted for commercial market introduction in North America, South America, and Asia. It will be available both as a stand-alone product and in a 1:2 mixture with saflufenacil. The herbicide is intended for use in preplant burndown and preemergence applications in cereal, corn (Zea mays L.), soybean [Glycine max (L.) Merr.], and pulse crops to control a variety of annual broadleaf and grass weed species. Additionally, it is intended to be used in tree crops, oil palm (Elaeis guineensis Jacq.), and non-crop areas. In this study, we meticulously evaluated the performance and effectiveness of both the stand-alone herbicide and the innovative mixture concept in combating prevalent weeds commonly encountered in corn and soybean fields. Our findings revealed that both products exhibited exceptional efficacy, significantly reducing the presence of these troublesome weeds. Furthermore, the mixture concept not only demonstrated commendable soil mobility but also showcased impressive residual activity, positioning it as a powerful tool for sustainable weed control. These promising effects are further substantiated by our comprehensive adsorption–distribution–metabolism–extraction (ADME) studies, which provide insight into the behavior and longevity of the herbicides in the agricultural ecosystem.
Synergistic Impact of Diurnal Warm Layers and Inertial Wave Mixing on Sea Surface Temperature Warming and Upper Ocean Stratification
Authors: Hsu Je‐Yuan , Chang Ming‐Huei , Jan Sen , Yang Yiing Jang
Published: November 2024

We study two sea surface temperature (SST) warming events and upper ocean stratification changes in the northern South China Sea in 2022 using data from an EM‐APEX float and satellite observations. The diurnal warm layers (DWLs) and the increasing buoyancy frequency N2 above the top of the thermocline can restrict the penetration depth of nighttime convection and wind‐driven mixing, which prevents cooler water from mixing upward, allowing solar heating to increase the SST by more than 1°C in a few days. The stratification budget approach is used to reproduce observations below 40 m despite some uncertainties in estimating variables such as horizontal gradient. After the first SST warming event, the stratification changes in the subsurface layers constituted by an increase in N2 above 70 m and a decrease below this depth can be attributed to the combined effects of turbulent diffusion and vertical advection rather than to horizontal advection or penetrative solar radiation. This ocean interior mixing is likely caused by the shear of near‐inertial waves at ∼50 m, when the nighttime convection could not penetrate through the DWL's base around 20 m. The stratification budget approach fails to simulate the changes above 40 m after the second SST warming event partly due to the presence of a near‐surface freshwater layer. Our observations offer insights into the effect of inertial wave‐induced mixing in the ocean interior when near‐surface stratified layers are present, which can lead to changes in upper ocean stratification and SST.
Organic Coatings Reduce Dissolution Rate by an Order of Magnitude for Carbonate Minerals Produced by Marine Fish
Authors: Oehlert Amanda M. , Walls Sarah , Arista Katelyn , Garza Jazmin , Folkerts Erik J. , Vitek Brooke E. , Tale Masoule Sadegh , Pollier Clément G. L. , Duchâtellier Gaëlle , Stieglitz John D. , Benetti Daniel D. , Heuer Rachael M. , Ghahremaninezhad Ali , Grosell Martin
Published: November 2024

Marine carbonate production and dissolution are important components of the global carbon cycle and the marine alkalinity budget. Global carbonate production by marine fish (ichthyocarbonate) has been estimated to be as high as 9.03 Pg CaCO3 yr−1; however, the fate of ichthyocarbonate is poorly understood. High magnesium concentrations in ichthyocarbonate would traditionally suggest rapid dissolution under current marine conditions, but a correlation between dissolution rate and mol%MgCO3 has not been observed. Here, we aim to determine the role of organic coatings on dissolution rates of ichthyocarbonate in marine environments. We applied a combination of petrographic, geochemical, and microCT approaches to assess the quantity and distribution of organic matter in ichthyocarbonate produced by two species of marine fish, the Gulf toadfish (Opsanus beta) and the Olive flounder (Paralichthys olivaceus). We show that organic matter, including external coatings and embedded organic material, is volumetrically significant, ranging from 8.5% to 32.3% of ichthyocarbonate by volume. Bleach oxidation of external organic matter coatings increased the dissolution rate of ichthyocarbonate by more than an order of magnitude, suggesting these coatings serve to reduce reactive surface area of the mineral fraction in ichthyocarbonate. Assuming that organic coatings do not influence sinking rates, external coatings extend the depth of ichthyocarbonate persistence in the water column by ∼12–15×. Therefore, organic coatings are an important determinant of the role of ichthyocarbonate in the marine carbon cycle.
Insights Into Magma Reservoir Dynamics From a Global Comparison of Volcanic and Plutonic Zircon Trace Element Variability in Individual Hand Samples
Authors: Ratschbacher Barbara C. , Keller C. Brenhin , Cooper Kari M.
Published: November 2024

Trace element compositional trends in zircons separated from single hand samples have been used to infer dynamic processes in magma reservoirs. Here, we compile published zircon trace element chemistry to quantify any systematic difference between the range of compositions observed in zircon from individual volcanic and plutonic hand samples and compare these results with geochemical modeling to derive implications for magma reservoir dynamics. We find that both rock types span a wide range of hand‐sample scale variability (i.e., wide range of coefficients of variation), but there is no systematic difference in the average variability between plutonic and volcanic samples (i.e., no difference in the mean coefficient of variation). This indicates that dynamic processes related to eruption are not necessarily required as a fundamental process to create hand sample‐scale compositional heterogeneity beyond what is present due to dynamic processes in the reservoir recorded in plutonic samples. Modeling of felsic systems (>68.5 wt.% SiO2) indicates that the similar average variability in felsic volcanic and plutonic hand samples cannot be reproduced by closed‐system crystallization of compositionally distinct melts locally within a magma reservoir (i.e., isolated melt pockets in a crystal mush) but requires mixing of at least two felsic melt compositions at a small spatial scale. This study provides a framework for focused studies on individual volcanic‐plutonic systems exploring how plutonic and volcanic zircon compositional variability records the time and length scales of magma reservoir processes.
McDonald Islands Phonolitic Lavas: Evidence for Zonation of the Kerguelen Plume
Authors: Fox J. M. , Falloon T. J. , Carey R. J. , Watson S. J. , Duncan R. A. , Olin P. H. , Arculus R. J. , Coffin M. F.
Published: November 2024

The McDonald Islands, together with Heard Island and the Kerguelen Archipelago, are volcanic islands on the mostly submerged Kerguelen Plateau, and the products of the long‐lived Kerguelen mantle plume (at least 130 Myr; Coffin et al., 2002, https://doi.org/10.25919/jw5f‐ad35). The first multibeam bathymetry data acquired around the Heard and McDonald islands reveal > 70 sea knolls surrounding the McDonald Islands and three sea knolls north of Heard Island. Rocks dredged from McDonald Islands sea knolls include fresh vesicular phonolitic lavas, phonolitic obsidian, phonolitic pillow fragments, and one basanite. These are the first phonolites sampled from the seafloor on the Kerguelen Plateau. Dredging of one sea knoll north of Heard Island recovered basaltic lavas. Lavas from the sea knolls are young, returning 40Ar/39Ar plateau ages of 73.7 ± 15.1 ka to 7.0 ± 2.7 ka for McDonald Islands sea knoll phonolites and 9.0 ± 1.3 ka for the Heard Island sea knoll. We define a new magma series, the McDonald Series, characterized by low εHf (−3.9 to −4.4) and lower Δ207Pb/204Pb (4.5–4.8) and Δ208Pb/204Pb (79–85) than all other lavas on the Kerguelen Plateau. This newly defined series is the product of a relatively young (Pleistocene‐Holocene) phase of volcanism produced by a distinct component of the Kerguelen mantle plume. We propose that McDonald Series phonolites together with 53.4 Ma lavas previously dredged from Ninetyeast Ridge provide evidence for zonation of the Kerguelen mantle plume.
Planetary Health Booms: Unpacking the Surge in Research Across the Globe Through Joint‐Point Analysis
Authors: Vaghela Gladson , Khan Zeeshan Ali , Elsheikh Randa , Makram Abdelrahman M. , Fatima Arshia , Makram Omar Mohamed , He Fei , Huy Nguyen Tien
Published: November 2024

Planetary Health (PH) is a relatively new field that studies the sciences behind the interaction between the environment, living organisms, and human health. The number of publications in this field has increased exponentially in the past few years. This study analyzed the trend of using the term “PH” in literature. We searched PubMed for all publications (APP) and those mentioning Planetary Health (APmPH) without limitations on text availability, dates, or species. The publication trend was estimated using the average annual percent change (AAPC). Joinpoint Regression Program 4.9.1.0 identified periods with statistically distinct log‐linear trends in publication numbers over time. Bonferroni adjustment determined significant trend shifts. The time frame of the retrieved APP and APmPH results ranged from 2002 to 2022 with a publication boom since 2017. The most common study designs were reviews, followed by comments and editorials. The APP, APmPH, and the proportion of APmPH to APP steadily increased from 2002 to 2022, with an AAPC of 6.0% (95% CI: 4.4%–7.6%, p < 0.001), 35.7 (95% CI: 21.3%–51.9%, p < 0.001), and 28.1% (95% CI: 15.2–42.5, p < 0.001), respectively. The term “PH” is increasingly prominent in academic literature, underscoring the need for interdisciplinary efforts. Its growing usage also highlights the need for recognition in Medical Subject Headings by the National Library of Medicine.
Iron Content‐Dependence of Ferropericlase Elastic Properties Across the Spin Crossover From Novel Experiments and Machine Learning
Authors: Trautner V. E. , Rijal A. , Plueckthun C. , Satta N. , Koemets E. , Buchen J. , Wang B. , Glazyrin K. , Cobden L. , Marquardt H.
Published: November 2024

The iron spin crossover in (Mg1‐xFex)O ferropericlase causes changes to its physical properties that are expected to affect seismic velocities in Earth's lower mantle. We present new time‐resolved pressure‐volume measurements of iron‐rich ferropericlase (xFe = 0.40, 0.59) and combine the results with literature data with xFe = 0.04–0.6 to investigate the dependence of ferropericlase elastic properties on iron content. We infer the relationship between unit‐cell volume, pressure and iron content directly from the data by training Mixture Density Networks and derive bulk modulus, density and bulk sound velocity from the outputs. This allows us to constrain the effect of the spin crossover on these properties and estimate their uncertainties for different iron contents. Our findings indicate that the spin crossover may significantly alter the physical properties of ferropericlase in iron‐enriched regions in the lowermost mantle, with implications for the interpretation of seismic heterogeneities observed near the core‐mantle boundary.
Baffin Bay Ice Export and Production From Sentinel‐1, the RADARSAT Constellation Mission, and CryoSat‐2: 2016–2022
Authors: Howell S. E. L. , Babb D. G. , Landy J. C. , Moore G. W. K. , Ballinger T. J. , McNeil K. , Montpetit B. , Brady M.
Published: November 2024

Baffin Bay is located between Greenland and several islands of the Canadian Arctic, providing a conduit for the downstream transport of ice and freshwater to the North Atlantic via Davis Strait. Using satellite observations from Sentinel‐1, the RADARSAT Constellation Mission, and CryoSat‐2, we estimated the sea ice export through Davis Strait and winter ice production in Baffin Bay from 2016 to 2022. The average annual ice export for this 6‐year period was 981 ± 193 × 103 km2 for area 816 ± 130 km3 for volume, and 653 ± 130 km3 for solid freshwater, all of which are considerably higher than previously reported estimates. The average winter ice area production upstream of Davis Strait was 758 × 103 km2 and the volume production was 589 km3 indicating that more than 80% of the ice exported out of Baffin Bay was produced locally. Compared to Fram Strait, sea ice fluxes through Davis Strait represent ∼59% of the volume and ∼111% of the area.
Dawn‐Dusk Asymmetry of the Magnetopause Distance Under the Parker Spiral Configuration of the IMF
Authors: Janda B. , Němec F. , Němeček Z. , Šafránková J.
Published: November 2024

The dawn‐dusk asymmetry of the magnetopause radial distance under the Parker (and ortho‐Parker) configuration of the interplanetary magnetic field (IMF) is investigated. An extensive data set of about 50,000 magnetopause crossings identified in the data from the THEMIS A‐E, Magion 4, Geotail, and Interball‐1 satellites is used for this purpose. It is shown that the magnetopause radial distances are larger at the side where the IMF is quasi‐parallel to the bow shock normal than at the side where IMF is quasi‐perpendicular to the bow shock normal. The effect is more significant at the flanks than close to the subsolar point. This introduces a significant asymmetry of the magnetopause shape, with the difference in the magnetopause radial distances being as large as about one Earth radius beyond the terminator. The experimental results are confirmed by a global magnetohydrodynamic (MHD) model, demonstrating that the asymmetry can be explained by MHD effects, without considering foreshock transients. This MHD model is further used to investigate the evolution of individual pressure components across the magnetopause and contrast them in quasi‐parallel and quasi‐perpendicular cases.
Influence of Ocean Currents on Wave Modeling and Satellite Observations: Insights From the One Ocean Expedition
Authors: Altiparmaki Ourania , Breivik Øyvind , Aouf Lotfi , Bohlinger Patrik , Johannessen Johnny A. , Collard Fabrice , Donlon Craig , Hope Gaute , Visser Pieter N. A. M. , Naeije Marc
Published: November 2024

This study investigates the influence of ocean currents on wave modeling and satellite observations using in situ wave measurements from the One Ocean Expedition 2021–2023. In January 2023, six OpenMetBuoy drifters were deployed in the Agulhas Current region. Their high immersion ratio minimized wind effects, allowing them to follow the current and return to the Indian Ocean by the Agulhas retroflection, collecting data for about 2 months. Comparing surface current velocities from both the Mercator model and Globcurrent product with drifter data reveals underestimation for velocities over with Mercator showing greater variability. Significant wave height and Stokes drift parameters from MFWAM and ERA5 were also evaluated against drifters. Both models tend to overestimate Stokes drift more noticeable in ERA5, indicating sensitivity to wind seas. For significant wave height, both models agree well with drifter measurements with correlations of 0.90 for MFWAM and 0.83 for ERA5. However, ERA5's lack of surface current data combined with its coarse resolution (0.5) lead to underestimation of wave heights exceeding 2.5 m. MFWAM products including and excluding currents exhibit root mean square errors of 0.39 and 0.45 m, respectively, when compared to drifter measurements. This confirms that neglecting currents introduces additional errors particularly in areas with sharp current gradients. Analyzing MFWAM wave spectra, including and excluding currents, reveals wave energy transfer attributed to wave‐current interactions. The spatial extent of these interactions is captured by satellite altimeters, revealing wave modulations with considerable wave height variations when waves cross eddies and the current core.
Using DIC‐δ13C Pair to Constrain Anthropogenic Carbon Increase in the Southeastern Atlantic Ocean Over the Most Recent Decade (2010–2020)
Authors: Gao Hui , Jin Meibing , Zhao Hui , Hussain Najid , Cai Wei‐Jun
Published: November 2024

The southeastern Atlantic Ocean is a crucial yet understudied region for the ocean absorption of anthropogenic carbon (Canth). Data from the A12 (2020) and A13.5 (2010) cruises offer an opportunity to examine changes in dissolved inorganic carbon (DIC), its stable isotope (δ13C), and Canth over the past decade within a limited region (1∼3°E, 32∼42°S). For the decade of 2010–2020, Canth invasion was observed from the sea surface down to 1,200 m based on both DIC and δ13C data. The mean Canth increase rate (1.08 ± 0.26 mol m−2 yr−1) during this period accelerated from 0.87 ± 0.05 mol m−2 yr−1 during the previous period (1983/84–2010). The δ13C‐based Canth increase closely matches the DIC‐based estimation below 500 m but is 26% higher in the upper ocean. This discrepancy is likely due to δ13C's longer air‐sea exchange timescale, seasonal variability in the upper ocean, and the chosen ratio of anthropogenically induced changes in δ13C and DIC. Finally, column inventory changes based on the two methods also exhibit very similar mean Canth uptake rates. The paired DIC concentration and stable isotope dataset may enhance our ability to constrain Canth accumulation and its controlling mechanisms in the ocean.
Unsteady Secondary Flow Structure at a Large River Confluence
Authors: Xu Lei , Yuan Saiyu , Vermeulen Bart , Qiu Jiajian , Jongbloed Henk , Tang Hongwu , Hoitink A. J. F.
Published: November 2024

River confluences, which are characterized by complex hydrodynamics, are key nodes for flood control and environmental protection. Two field surveys were carried out at the confluence of the Yangtze River and Poyang Lake to investigate the transient character of flow structures, which are often assumed steady. Repeat‐transect acoustic Doppler current profile measurements were processed and analyzed, adopting a new method to separate mean flow from turbulence and measurement error based on physics‐informed generalized Tikhonov regularization. The two field surveys were characterized by two distinct mixing interface modes: A so‐called Kelvin–Helmholtz (KH) mode, and a wake mode. In KH mode, large‐scale flow fluctuations were observed. These flow fluctuations exert a substantial influence on the alternation of secondary flows by changing the water surface pressure gradient, affecting the intensity of secondary flows rather than their spatial structure. We infer that temperature‐induced stratification is the main cause of this. In the wake mode, multiple vortices in the wake region at the confluence apex also produced flow fluctuations, directly related to the primary velocity gradient. We argue that even for constant incoming flows, secondary flow at river confluences can exhibit channel‐scale unsteadiness related to migration of the turbulent mixing interface. Our findings highlight the crucial role of density effects in regulating secondary flow unsteadiness, which is essential for understanding contaminant and sediment dispersal in river systems.
Early progressive mobility to improve neurodevelopment of infants with severe bronchopulmonary dysplasia at a level IV neonatal intensive care unit: a prospective cohort study
Authors: Morris Heidi , Nilan Kathleen , Burkhardt Meghan , Wood Audrey , Passarella Molly , Gibbs Kathleen , DeMauro Sara B.
Published: November 2024

Objective

To measure the feasibility of early progressive mobility (EPM) in intubated infants with severe bronchopulmonary dysplasia (BPD) and compare neurodevelopmental skill acquisition of these infants before and after implementation of a clinical EPM program.

Study design

Single-center pre-post intervention prospective cohort study in a level IV Neonatal Intensive Care Unit (NICU) from 2019–2022. Bivariate tests compared EPM interventions and results of serial Test of Infant Motor Performance (TIMP) assessments in 32 intubated infants with severe BPD cared for during two epochs, before and after NICU-wide EPM implementation.

Results

Infants in epoch 2 experienced significantly more EPM interventions than infants in epoch 1. Infants in epoch 2 also had more advanced motor skills on the TIMP than infants in epoch 1. There were no unplanned extubations.

Conclusions

We demonstrated successful implementation of EPM in this high-risk population with evidence of beneficial impacts on early motor development.
A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones
Authors: Sánchez-Lanzas Raúl , Barclay Justin , Hardas Alexandros , Kalampalika Foteini , Jiménez-Pompa Amanda , Gallipoli Paolo , Ganuza Miguel
Published: November 2024

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice. Provocatively, germline NOTCH3 ECD mutations perturbing cysteine numbers cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a type of vascular dementia, suggesting an unexpected link between CADASIL and CH. Here, we formally demonstrated that mouse hematopoietic stem and progenitor cells (HSPCs) expressing CADASIL-related NOTCH3

C455R
exhibit a proliferative advantage resulting in robust cellular expansion in vivo and in vitro. Co-expression of NOTCH3

C455R
and Dnmt3a

R878H
, homologous to a frequent human CH mutation, increased the fitness of NOTCH3

C455R
HSPCs, demonstrating their functional cooperation. Surprisingly, the presence of NOTCH3

C455R
hematopoietic cells supported the expansion of Dnmt3a

R878H
HSPCs in a non-cell autonomous fashion in vivo, strongly suggesting that CADASIL patients and asymptomatic carriers can be highly predisposed to DNMT3A

R882H
-driven CH. Considering that CADASIL-related NOTCH3 mutations are more frequent in the general population than anticipated (~1 carrier in 400 people), the effect of these NOTCH3 mutations on CH development should be considered.
Defect-insensitive cylindrical surface lattice resonance array and its batch replication for enhanced immunoassay
Authors: Zhou Bin , Hu Chao , Li Haoyang , Ye Xiangyi , Wen Baohua , Zhou Zhangkai , Cai Jingxuan , Zhou Jianhua
Published: November 2024

Surface lattice resonances (SLR) have been demonstrated to enhance the sensitivity and reduce the full width at half maximum (FWHM) of the plasmonic resonances. However, their widespread application in immunoassays has been hindered by limitations of high structural defect sensitivity and fabrication costs. Here, we design a novel three-layer cylindrical SLR array that exhibits high tolerance against structural defects, which would facilitate straightforward fabrication. By integrating metal evaporation and nanoimprint lithography, we demonstrate the replication of the SLR array with exceptional quality. Theoretical simulations indicate that the resonance dips of these arrays exhibit are not sensitive to various structural defects. The experimental results reveal that the FWHM of these arrays can be as low as 5.1 nm while maintaining robust resonance characteristics. Furthermore, we demonstrated the high spectral sensitivity of the SLR array, which enabled the detection of immunoglobulin G (IgG) at concentrations as low as 609 pg/mL. These findings emphasize the potential of the defect-insensitive SLR array as a highly scalable immunoassay platform with exceptional performance.
The abscopal effects of sonodynamic therapy in cancer
Authors: Collins Victoria G. , Hutton Dana , Hossain-Ibrahim Kismet , Joseph James , Banerjee Sourav
Published: November 2024

The abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced ‘vaccine-effect’ as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.
An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death
Authors: Eom Jae-Won , Lee Jin-Yeon , Kwon Yeabin , Kim Yang-Hee
Published: November 2024

In the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF’s neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF’s protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H2O2) and 1-methyl-4-phenylpyridinium ion (MPP+). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation.
STING orchestrates microglia polarization via interaction with LC3 in autophagy after ischemia
Authors: Kong Lingqi , Xu Pengfei , Shen Nan , Li Wenyu , Li Rui , Tao Chunrong , Wang Guoping , Zhang Yan , Sun Wen , Hu Wei , Liu Xinfeng
Published: November 2024

Autophagy has both protective and pathogenetic effects on injury caused by cerebral ischemia/reperfusion (I/R). Our previous research has indicated that stimulator of interferon genes (STING) could orchestrate microglia polarization following middle cerebral artery occlusion. However, it remains largely unexplored whether STING balances microglial polarization by regulating autophagy in brain I/R injury. Here, STING was observed to show an up-regulation in the microglia from mice subjected to experimental ischemic stroke. Strikingly, the deletion of STING led to the significant skewness of microglia activated by ischemia from a pro- to anti-inflammatory state and substantially alleviated ischemia-induced infarction and neuronal injury. In addition, STING-null mice can restore long-term neurobehavioral function. Then, the crosstalk between neuroinflammation and microglia autophagy was analyzed. The differential activity of autophagy in wild-type and STING-knockout (KO) mice or primary microglia was largely reversed when STING was restored in microglia. Irritating autophagy by rapamycin skewed the anti‑inflammatory state induced by STING-KO to a pro‑inflammatory state in microglia. Furthermore, microtubule-associated protein light-chain-3 (LC3) was identified as the key factor in the STING regulation of autophagy by glutathione-S-transferase (GST) pull-down analysis. Mechanically, STING can directly interact with LC3 through the STING transmembrane domain (1-139aa). Herein, current data determine the pivotal role of autophagy, specifically via LC3 protein, in the regulation of microglial phenotypic transformation by STING. These findings may provide a possible treatment target for delaying the progression of ischemic stroke.
Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes
Authors: Alcalde-Herraiz Marta , Xie JunQing , Newby Danielle , Prats Clara , Gill Dipender , Gordillo-Marañón María , Prieto-Alhambra Daniel , Català Martí , Prats-Uribe Albert
Published: November 2024

Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.
Data-driven design of novel lightweight refractory high-entropy alloys with superb hardness and corrosion resistance
Authors: Gao Tianchuang , Gao Jianbao , Yang Shenglan , Zhang Lijun
Published: November 2024

Lightweight refractory high-entropy alloys (LW-RHEAs) hold significant potential in the fields of aviation, aerospace, and nuclear energy due to their low density, high strength, high hardness, and corrosion resistance. However, the enormous composition space has severely hindered the development of novel LW-RHEAs with excellent comprehensive performance. In this paper, an machine learning (ML)-based alloy design strategy combined with a multi-objective optimization method was proposed and applied for a rational design of Al-Nb-Ti-V-Zr-Cr-Mo-Hf LW-RHEAs. The quantitative relation of “composition-structure-property” was first established by ML modeling. Then, feature analysis reveals that Cr content greater than 12 at.% is a key criterion for alloys with high corrosion resistance. The phase structure, density, melting point, hardness and corrosion resistance of the alloys were screened layer by layer, and finally, three LW-RHEAs with superb hard and corrosion resistance were successfully designed. Key experimental validation indicates that three target alloys have densities around 6.5 g/cm3, and all alloys are disordered bcc_A2 single-phase with the highest hardness of 593 HV and the largest pitting potential of 2.5 VSCE, which far exceeds all the literature reports. The successful demonstration in this paper clearly demonstrates that the present design strategy driven by the ML technique should be generally applicable to other RHEA systems.
Systematic screening of 42 vancomycin-resistant Enterococcus faecium strains for resistance, biofilm, and desiccation in simulated microgravity
Authors: Arndt Franca , Siems Katharina , Walker Sarah V. , Bryan Noelle C. , Leuko Stefan , Moeller Ralf , Boschert Alessa L.
Published: November 2024

Vancomycin-resistant Enterococcus faecium (VRE) presents significant challenges in healthcare, particularly for hospitalized and immunocompromised patients, including astronauts with dysregulated immune function. We investigated 42 clinical E. faecium isolates in simulated microgravity (sim. µg) using a 2-D Clinostat, with standard gravity conditions (1 g) as a control. Isolates were tested against 22 antibiotics and characterized for biofilm formation and desiccation tolerance. Results showed varied responses in minimum inhibitory concentration (MIC) values for seven antibiotics after sim. µg exposure. Additionally, 55% of isolates showed a trend of increased biofilm production, and 59% improved desiccation tolerance. This investigation provides initial insights into E. faecium’s changes in response to simulated spaceflight, revealing shifts in antibiotic resistance, biofilm formation, and desiccation tolerance. The observed adaptability emphasizes the need to further understand VRE’s resilience to microgravity, which is crucial for preventing infections and ensuring crew health on future long-duration space missions.
Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data
Authors: Chou Renee Ti , Ouattara Amed , Takala-Harrison Shannon , Cummings Michael P.
Published: November 2024

Intensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens based on features of known antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of only the unlabeled proteins from the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.
Cretaceous bird from Brazil informs the evolution of the avian skull and brain
Authors: Chiappe Luis M. , Navalón Guillermo , Martinelli Agustín G. , Carvalho Ismar de Souza , Miloni Santucci Rodrigo , Wu Yun-Hsin , Field Daniel J.
Published: November 2024

A dearth of Mesozoic-aged, three-dimensional fossils hinders understanding of the origin of the distinctive skull and brain of modern (crown) birds1. Here we report Navaornis hestiae gen. et sp. nov., an exquisitely preserved fossil species from the Late Cretaceous of Brazil. The skull of Navaornis is toothless and large-eyed, with a vaulted cranium closely resembling the condition in crown birds; however, phylogenetic analyses recover Navaornis in Enantiornithes, a highly diverse clade of Mesozoic stem birds. Despite an overall geometry quantitatively indistinguishable from crown birds, the skull of Navaornis retains numerous plesiomorphies including a maxilla-dominated rostrum, an akinetic palate, a diapsid temporal configuration, a small cerebellum and a weakly expanded telencephalon. These archaic neurocranial traits are combined with a crown bird-like degree of brain flexion and a bony labyrinth comparable in shape to those of many crown birds but substantially larger. Altogether, the emergent cranial geometry of Navaornis shows an unprecedented degree of similarity between crown birds and enantiornithines, groups last sharing a common ancestor more than 130 million years ago2. Navaornis provides long-sought insight into the detailed cranial and endocranial morphology of stem birds phylogenetically crownward of Archaeopteryx, clarifying the pattern and timing by which the distinctive neuroanatomy of living birds was assembled.
Fluorspar to fluorochemicals upon low-temperature activation in water
Authors: Klose Immo , Patel Calum , Mondal Anirban , Schwarz Andrew , Pupo Gabriele , Gouverneur Véronique
Published: November 2024

The dangerous chemical hydrogen fluoride sits at the apex of the fluorochemical industry, but the substantial hazards linked to its production under harsh conditions (above 300 degrees Celsius) and transport are typically contracted to specialists. All fluorochemicals for applications, including refrigeration, electric transportation, agrochemicals and pharmaceuticals, are prepared from fluorspar (CaF2) through a procedure that generates highly dangerous hydrogen fluoride1–5. Here we report a mild method to obtain fluorochemicals directly from fluorspar, bypassing the necessity to manufacture hydrogen fluoride. Acid-grade fluorspar (more than 97 per cent CaF2) is treated with the fluorophilic Lewis acid boric acid (B(OH)3) or silicon dioxide (SiO2), in the presence of oxalic acid, a Brønsted acid that is highly effective for Ca2+ sequestration. This scalable process carried out in water at low temperature (below 50 degrees Celsius) enables access to widely used fluorochemicals, including tetrafluoroboric acid, alkali metal fluorides, tetraalkylammonium fluorides and fluoro(hetero)arenes. The replacement of oxalic acid with sulfuric acid gave comparable results for B(OH)3, but was not as effective when the fluorophilic Lewis acid was SiO2. A similar process also works with the lower-purity metspar. The production of fluorochemicals directly from fluorspar offers the possibility of decentralized manufacturing—an attractive model for the fluorochemical industry. With the renewed interest in innovative methods to synthesize oxalic acid via carbon dioxide capture and biomass6,7, and the challenges posed by our dependence on fossil fuels for sulfur and therefore sulfuric acid supply8,9, our technology may represent a departure towards a sustainable fluorochemical industry.
Adult skull bone marrow is an expanding and resilient haematopoietic reservoir
Authors: Koh Bong Ihn , Mohanakrishnan Vishal , Jeong Hyun-Woo , Park Hongryeol , Kruse Kai , Choi Young Jun , Nieminen-Kelhä Melina , Kumar Rahul , Pereira Raquel S. , Adams Susanne , Lee Hyuek Jong , Bixel M. Gabriele , Vajkoczy Peter , Krause Daniela S. , Adams Ralf H.
Published: November 2024

The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate1. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis2, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of bone marrow in adult and ageing skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total haematopoietic output. Furthermore, skull is largely protected against major hallmarks of ageing, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Conspicuous rapid and dynamic changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukaemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbours a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies and, potentially, for clinical treatments in humans.