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Abstract Background The secretome of primary bovine mammosphere-derived epithelial cells (MDECs) has been shown to exert antimicrobial, regenerative, and immunomodulatory properties in vitro, which warrants its study as a potential biologic treatment with the potential to be translated to human medicine. Currently, the use of the MDEC secretome as a therapy is constrained by the limited life span of primary cell cultures and the decrease of secretome potency over cell passages. Methods To address these limitations, early-passage bovine MDECs were immortalized using hTERT, a human telomerase reverse transcriptase. The primary and immortal MDECs were compared morphologically, transcriptomically, and phenotypically. The functional properties and proteomic profiles of the secretome of both cell lines were evaluated and compared. All experiments were performed with both low and high passage cell cultures. Results We confirmed through in vitro experiments that the secretome of immortalized MDECs, unlike that of primary cells, maintained antimicrobial and pro-migratory properties over passages, while pro-angiogenic effects of the secretome from both primary and immortalized MDECs were lost when the cells reached high passage. The secretome from primary and immortalized MDECs, at low and high passages exerted immunomodulatory effects on neutrophils in vitro. Conclusions High passage immortalized MDECs retain a bioactive secretome with antimicrobial, regenerative, and immunomodulatory properties, suggesting they may serve as a consistent cell source for therapeutic use.

Abstract Nitride ferroelectrics have recently emerged as promising alternatives to oxide ferroelectrics due to their compatibility with mainstream semiconductor processing. ScAlN, in particular, has exhibited remarkable piezoelectric coupling strength (K 2) comparable to that of lithium niobate, making it a valuable choice for RF filters in wireless communications. Recently, ScAlN has sparked interest in its use for nanophotonic devices, chiefly due to its large bandgap facilitating operation in blue wavelengths coupled with promises of enhanced nonlinear optical properties such as a large second-order susceptibility (χ (2)). It is still an open question whether ScAlN can outperform oxide ferroelectrics concerning the Pockels effect—an electro-optic coupling extensively utilized in optical communications devices. In this paper, we present a comprehensive theoretical analysis and experimental demonstration of ScAlN’s Pockels effect. Our findings reveal that the electro-optic coupling of ScAlN, despite being weak at low Sc concentration, may be significantly enhanced and exceed LiNbO3 at high levels of Sc doping, which points the direction of continued research efforts to unlock the full potential of ScAlN.

Latent growth curve modeling was used to investigate the longitudinal link between attachment, effortful control (EC), and maladaptive development during middle childhood. In a community sample, children (Time 1: n = 157; M[subscript age] = 10.91) and their mothers were examined three times over a two-year period. Attachment was operationalized at a more strategic (self-reported trust in maternal support) and more automatic level (secure base script knowledge). Mothers reported about children's EC and maladjustment. Secure attachment was associated with higher EC, but EC development was only linked with baseline self-reported trust. Also, EC indirectly linked baseline self-reported trust with change in externalizing and internalizing problems over time. In addition, self-reported trust was indirectly linked with change in externalizing problems over time through EC development. EC, and, less robustly, EC development were linked with attachment and change in emotional and behavioral problems.

Mesoscale weather systems cause spatiotemporal variability in offshore wind power, and insight into their fluctuations can support grid operations. In this study, a 10-year model integration with the kilometre-scale atmospheric model COnsortium for Small-scale MOdelling – CLimate Mode (COSMO-CLM) provided a wind and potential power fluctuation analysis in the Kattegat, a midlatitude sea strait with a width of 130 km and an irregular coastline. The model agrees well with scatterometer data away from coasts and small islands, with a spatiotemporal root-mean square difference of 1.35 m s−1. A comparison of 10 min wind speed at about 100 m with lidar data for a 2-year period reveals very good performance, with a slight model overestimation of 0.08 m s−1 and a high value for the Perkins skill score (0.97). From periodograms made using the Welch's method, it was found that the wind speed variability on a sub-hourly timescale is higher in winter compared to summer. In contrast, the wind power varies more in summer when winds often drop below the rated power threshold. During winter, variability is largest in the northeastern part of the Kattegat due to a spatial spin-up of convective systems over the sea during the predominant southwesterly winds. Summer convective systems are found to develop over land, driving spatial variability in offshore winds during this season. On average over the 10 summers, the mesoscale wind speeds are up to 20 % larger than the synoptic background at 17:00 UTC with a clear diurnal cycle. The winter-averaged mesoscale wind component is up to 10 % larger, with negligible daily variation. Products with a lower resolution like ERA5 substantially underestimate this ratio between the mesoscale and synoptic wind speed. Moreover, taking into account mesoscale spatial variability is important for correctly representing temporal variability in power production. The root-mean square difference between two power output time series, one ignoring and one accounting for mesoscale spatial variability, is 14 % of the total power generation.

As many coastal regions experience a rapid increase in offshore wind farm installations, inter-farm distances become smaller, with a tendency to install larger turbines at high capacity densities. It is, however, not clear how the wake losses in wind farm clusters depend on the characteristics and spacing of the individual wind farms. Here, we quantify this based on multiple COSMO-CLM simulations, each of which assumes a different, spatially invariant combination of the turbine type and capacity density in a projected, future wind farm layout in the North Sea. An evaluation of the modelled wind climate with mast and lidar data for the period 2008–2020 indicates that the frequency distributions of wind speed and wind direction at turbine hub height are skillfully modelled and the seasonal and inter-annual variations in wind speed are represented well. The wind farm simulations indicate that for a typical capacity density and for SW winds, inter-farm wakes can reduce the capacity factor at the inflow edge of wind farms from 59 % to between 54 % and 30 % depending on the proximity, size and number of the upwind farms. The efficiency losses due to intra- and inter-farm wakes become larger with increasing capacity density as the layout-integrated, annual capacity factor varies between 51.8 % and 38.2 % over the considered range of 3.5 to 10 MW km−2. Also, the simulated efficiency of the wind farm layout is greatly impacted by switching from 5 MW turbines to next-generation, 15 MW turbines, as the annual energy production increases by over 27 % at the same capacity density. In conclusion, our results show that the wake losses in future wind farm clusters are highly sensitive to the inter-farm distances and the capacity densities of the individual wind farms and that the evolution of turbine technology plays a crucial role in offsetting these wake losses.

In Quebec, the Act Respecting Threatened or Vulnerable species (ARTV), adopted in 1989, aims to safeguard Quebec's wild genetic diversity by protecting species at risk. However, since its implementation about 30 years ago, it has been repeatedly pointed out that the application of the Quebec legislative framework for the protection of wildlife species at risk was often slow and inadequate. The aim of this article is therefore to make a series of observations on the limits of current legislation and then propose nine urgent recommendations to improve the effectiveness of conservation efforts for species at risk in Quebec. Our recommendations aim to increase the efficiency and transparency of the designation process, reconsider compensation mechanisms for the loss of critical habitat, and harmonize species status between the federal and provincial levels. We hope that our article will pave the way for a constructive discussion leading to an improved protection of wildlife species in precarious situations and their persistence for future generations. The English version of this article is available in the Supplementary material file.

The coherence times of state-of-the-art superconducting qubits are limited by bulk dielectric loss, yet the microscopic mechanism leading to this loss is unclear. Here, we propose that the experimentally observed loss can be attributed to the presence of charged defects that enable the absorption of electromagnetic radiation by the emission of acoustic phonons. Our explicit derivation of the absorption coefficient for this mechanism allows us to derive a loss tangent of 7.2 × 10−9 for Al2O3, in good agreement with recent high-precision measurements [Read et al., Phys. Rev. Appl. 19, 034064 (2023)]. We also find that for temperatures well below ∼0.2 K, the loss should be independent of temperature, which is also in agreement with observations. Our investigations show that the loss per defect depends mainly on properties of the host material, and a high-throughput search suggests that diamond, cubic BN, AlN, and SiC are optimal in this respect.

Single-photon emitters are an essential component of quantum networks, and defects or impurities in semiconductors are a promising platform to realize such quantum emitters. Here, we present a model that encapsulates the essential physics of coupling to phonons, which governs the behavior of real single-photon emitters, and critically evaluate several approximations that are commonly utilized. Emission in the telecom wavelength range is highly desirable, but our model shows that nonradiative processes are greatly enhanced at these low photon energies, leading to a decrease in efficiency. Our results suggest that reducing the phonon frequency is a fruitful avenue to enhance the efficiency.

BackgroundInnovative therapies against bacterial infections are needed. One approach is to focus on host-directed immunotherapy (HDT), with treatments that exploit natural processes of the host immune system. The goals of this type of therapy are to stimulate protective immunity while minimizing inflammation-induced tissue damage. We use non-traditional large animal models to explore the potential of the mammosphere-derived epithelial cell (MDEC) secretome, consisting of all bioactive factors released by the cells, to modulate host immune functions. MDEC cultures are enriched for mammary stem and progenitor cells and can be generated from virtually any mammal. We previously demonstrated that the bovine MDEC secretome, collected and delivered as conditioned medium (CM), inhibits the growth of bacteria in vitro and stimulates functions related to tissue repair in cultured endothelial and epithelial cells.MethodsThe immunomodulatory effects of the bovine MDEC secretome on bovine neutrophils, an innate immune cell type critical for resolving bacterial infections, were determined in vitro using functional assays. The effects of MDEC CM on neutrophil molecular pathways were explored by evaluating the production of specific cytokines by neutrophils and examining global gene expression patterns in MDEC CM-treated neutrophils. Enzyme linked immunosorbent assays were used to determine the concentrations of select proteins in MDEC CM and siRNAs were used to reduce the expression of specific MDEC-secreted proteins, allowing for the identification of bioactive factors modulating neutrophil functions.ResultsNeutrophils exposed to MDEC secretome exhibited increased chemotaxis and phagocytosis and decreased intracellular reactive oxygen species and extracellular trap formation, when compared to neutrophils exposed to control medium. C-X-C motif chemokine 6, superoxide dismutase, peroxiredoxin-2, and catalase, each present in the bovine MDEC secretome, were found to modulate neutrophil functions.ConclusionThe MDEC secretome administered to treat bacterial infections may increase neutrophil recruitment to the site of infection, stimulate pathogen phagocytosis by neutrophils, and reduce neutrophil-produced ROS accumulation. As a result, pathogen clearance might be improved and local inflammation and tissue damage reduced.

Abstract Mammary cancer incidence varies greatly across species and underlying mechanisms remain elusive. We previously showed that mammosphere-derived epithelial cells from species with low mammary cancer incidence, such as horses, respond to carcinogen 7, 12-Dimethylbenz(a)anthracene-induced DNA damage by undergoing apoptosis, a postulated anti-cancer mechanism. Additionally, we found that miR-214-3p expression in mammosphere-derived epithelial cells is lower in mammary cancer-resistant as compared to mammary cancer-susceptible species. Here we show that increasing miR-214 expression and decreasing expression of its target gene nuclear factor kappa B subunit 1 in mammosphere-derived epithelial cells from horses abolishes 7,12-Dimethylbenz(a)anthracene-induced apoptosis. A direct interaction of miR-214-3p with another target gene, unc-5 netrin receptor A, is also demonstrated. We propose that relatively low levels of miR-214 in mammosphere-derived epithelial cells from mammals with low mammary cancer incidence, allow for constitutive gene nuclear factor kappa B subunit 1 expression and apoptosis in response to 7, 12-Dimethylbenz(a)anthracene. Better understanding of the mechanisms regulating cellular responses to carcinogens improves our overall understanding of mammary cancer resistance mechanisms.

Variations in local strain, defect densities, and composition of hybrid metal-halide perovskites have been reported to create heterogeneous energy landscapes in thin films, which impact charge-carrier diffusion and recombination dynamics. Here, we employ one- and two-photon transient absorption spectroscopy to selectively probe the dynamics of charge carriers from surface and bulk regions of methylammonium lead bromide thin films. Differences in the transient absorption spectra indicate that an energy gradient of approximately 100 meV is formed between the higher band-gap surface and lower band-gap bulk regions. Thus, during their lifetime, photoexcited carriers move away from the surface to recombine in the bulk, where our experiments detect long-lived charge populations despite the significant band splitting that has conventionally been assumed to inhibit efficient radiative recombination. Supported by first-principles calculations, we demonstrate that bright emission can still arise from the bulk with states that occupy a wide range of momenta in the vicinity of the band extrema, which show strong dipole transitions. Our results report that photoexcitations in the hybrid perovskites avoid defect-rich surface regions, and that particularly strong emission is generated from accumulated excitation populations in the bulk.

First-principles calculations of defects and electron–phonon interactions play a critical role in the design and optimization of materials for electronic and optoelectronic devices. The late Audrius Alkauskas made seminal contributions to developing rigorous first-principles methodologies for the computation of defects and electron–phonon interactions, especially in the context of understanding the fundamental mechanisms of carrier recombination in semiconductors. Alkauskas was also a pioneer in the field of quantum defects, helping to build a first-principles understanding of the prototype nitrogen-vacancy center in diamond, as well as identifying novel defects. Here, we describe the important contributions made by Alkauskas and his collaborators and outline fruitful research directions that Alkauskas would have been keen to pursue. Audrius Alkauskas' scientific achievements and insights highlighted in this article will inspire and guide future developments and advances in the field. [ABSTRACT FROM AUTHOR]

Abstract The bovine mammary stem/progenitor cell secretome stimulates regeneration in vitro and contains proteins associated with antimicrobial defense. This has led to the exploration of the secretome as a biologic treatment for mastitis, a costly inflammation of the udder commonly caused by bacteria. This study reports on a population of bovine mammary stem/progenitor cells isolated non-invasively from milk (MiDCs). MiDCs were characterized by immunophenotyping, mammosphere formation assays, and single cell RNA sequencing. They displayed epithelial morphology, exhibited markers of mammary stem/progenitor cells, and formed mammospheres, like mammary gland tissue-isolated stem/progenitor cells. Single cell RNA sequencing revealed two sub-populations of MiDCs: epithelial cells and macrophages. Functionally, the MiDC secretome increased fibroblast migration, promoted angiogenesis of endothelial cells, and inhibited the growth of mastitis-associated bacteria, including antibiotic-resistant strains, in vitro. These qualities of MiDCs render them a source of stem cells and stem cell products that may be used to treat diseases affecting the dairy industry, including mastitis.

Abstract The Fe(II)-induced ferroptotic cell death pathway is an asset in cancer therapy, yet it calls into question the biocompatibility of magnetic nanoparticles. In the latter, Fe(II) is sequestered within the crystal structure and is released only upon nanoparticle degradation, a transition that is not well understood. Here, we dissect the chemical environment necessary for nanoparticle degradation and subsequent Fe(II) release. Importantly, temperature acts as an accelerator of the process and can be triggered remotely by laser-mediated photothermal conversion, as evidenced by the loss of the nanoparticles’ magnetic fingerprint. Remarkably, the local hot-spot temperature generated at the nanoscale can be measured in operando, in the vicinity of each nanoparticle, by comparing the photothermal-induced nanoparticle degradation patterns with those of global heating. Further, remote photothermal irradiation accelerates degradation inside cancer cells in a tumor spheroid model, with efficiency correlating with the endocytosis progression state of the nanoparticles. High-throughput imaging quantification of Fe2+ release, ROS generation, lipid peroxidation and cell death at the spheroid level confirm the synergistic thermo-ferroptotic therapy due to the photothermal degradation at the nanoparticle level.

In 2021, Nigeria witnessed a severe cholera outbreak that affected Borno state, in which more than 1,600,000 internally displaced persons (IDPs) resided at the time. This rapid appraisal explored factors that facilitate the recurrence of cholera outbreaks in sites hosting IDPs in Northeast Nigeria. Semi-structured interviews were conducted with water, sanitation, and hygiene (WASH), management, and healthcare personnel working in ten displacement camps in Borno state. The interviews were complemented by transect walks and field observations, measurements of free residual chlorine levels, and publicly available data published by the International Organization for Migration Displacement Tracking Matrix. The recurrence of cholera outbreaks appears to be facilitated by substantial interactions between IDPs and host communities, and suboptimal WASH services in camps. Of particular concern, IDP camps are exposed to extreme weather-related events that damage facilities and subsequently affect WASH practices. WASH services in camps may likewise be severely hindered by an influx of new arrivals. In conclusion, we emphasize the importance of expanding WASH activities to host communities and developing site-specific WASH interventions and chlorination targets. Practical recommendations are needed for the prevention and control of outbreaks following extreme weather-related events and population influxes. HIGHLIGHTS Challenges to the prevention and control of cholera in displacement camps are especially pronounced following shocks.; Strategies are likely to be more effective when targeting both camps and host communities.; Site-specific chlorination targets are needed to maintain adequate free residual chlorine levels throughout the year.; Interventions must be contextualized and developed through a participatory approach.;

Abstract Introduction Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin‐2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio‐target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. Methods and results Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial‐to‐mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient‐derived xenograft models. Using an oligonucleotide anti‐sense anti‐PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop. Conclusion Our results open the way for further studies using PROM2 as a bio‐target in resort situations in human metastatic melanoma and also in other cancer types.

Introduction Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG.Methods and analysis 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m2 on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life.Ethics and dissemination The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences.Trial registration number NCT04911621

Summary: Mesenchymal stromal cells (MSCs) have the potential to be used as therapeutics, but their efficacy varies due to cellular heterogeneity, which is not fully understood. After characterizing donor-matched bovine MSC from adipose tissue (AT), bone marrow (BM), and peripheral blood (PB), we performed single-cell RNA sequencing (scRNA-seq) to evaluate overarching similarities and differences across these three tissue-derived MSCs. Next, the transcriptomic profiles of the bovine MSCs were compared to those of equine MSCs, derived from the same tissue sources and previously published by our group, and revealed species-specific differences. Finally, the transcriptomic profile from bovine BM-MSCs was compared to mouse and human BM-MSCs and demonstrated that bovine BM-MSCs share more common functionally relevant gene expression profiles with human BM-MSCs than compared to murine BM-MSCs. Collectively, this study presents the cow as a potential non-traditional animal model for translational MSC studies based on transcriptomic profiles similar to human MSCs.

Abstract In terrestrial and marine ecosystems, migrants from protected areas may buffer the risk of harvest‐induced evolutionary changes in exploited populations that face strong selective harvest pressures. Understanding the mechanisms favoring genetic rescue through migration could help ensure evolutionarily sustainable harvest outside protected areas and conserve genetic diversity inside those areas. We developed a stochastic individual‐based metapopulation model to evaluate the potential for migration from protected areas to mitigate the evolutionary consequences of selective harvest. We parameterized the model with detailed data from individual monitoring of two populations of bighorn sheep subjected to trophy hunting. We tracked horn length through time in a large protected and a trophy‐hunted populations connected through male breeding migrations. We quantified and compared declines in horn length and rescue potential under various combinations of migration rate, hunting rate in hunted areas and temporal overlap in timing of harvest and migrations, which affects the migrants' survival and chances to breed within exploited areas. Our simulations suggest that the effects of size‐selective harvest on male horn length in hunted populations can be dampened or avoided if harvest pressure is low, migration rate is substantial, and migrants leaving protected areas have a low risk of being shot. Intense size‐selective harvest impacts the phenotypic and genetic diversity in horn length, and population structure through changes in proportions of large‐horned males, sex ratio and age structure. When hunting pressure is high and overlaps with male migrations, effects of selective removal also emerge in the protected population, so that instead of a genetic rescue of hunted populations, our model predicts undesirable effects inside protected areas. Our results stress the importance of a landscape approach to management, to promote genetic rescue from protected areas and limit ecological and evolutionary impacts of harvest on both harvested and protected populations.

Palm oil (PO), a semi-solid fat at room temperature, is a popular food ingredient. To steer the fat functionality, sucrose esters (SEs) are often used as food additives. Many SEs exist, varying in their hydrophilic-to-lipophilic balance (HLB), making them suitable for various food and non-food applications. In this study, a stearic–palmitic sucrose ester with a moderate HLB (6) was studied. It was found that the SE exhibited a complex thermal behavior consistent with smectic liquid crystals (type A). Small-angle X-ray scattering revealed that the mono- and poly-esters of the SE have different packings, more specifically, double and single chain-length packing. The polymorphism encountered upon crystallization was repeatable during successive heating and cooling cycles. After studying the pure SE, it was added to palm oil, and the crystallization behavior of the mixture was compared to that of pure palm oil. The crystallization conditions were varied by applying cooling at 20 °C/min (fast) and 1 °C/min (slow) to 0 °C, 20 °C or 25 °C. The samples were followed for one hour of isothermal time. Differential scanning calorimetry (DSC) showed that nucleation and polymorphic transitions were accelerated. Wide-angle X-ray scattering (WAXS) unraveled that the α-to-β′ polymorphic transition remained present upon the addition of the SE. SAXS showed that the addition of the SE at 0.5 wt% did not significantly change the double chain-length packing of palm oil, but it decreased the domain size when cooling in a fast manner. Ultra-small-angle X-ray scattering (USAXS) revealed that the addition of the SE created smaller crystal nanoplatelets (CNPs). The microstructure of the fat crystal network was visualized by means of polarized light microscopy (PLM) and cryo-scanning electron microscopy (cryo-SEM). The addition of the SE created a finer and space-filling network without the visibility of separate floc structures.