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Abstract The apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.

This paper documents the methodology and preliminary results from a perturbed parameter ensemble (PPE) technique, where multiple parameters are varied simultaneously and the parameter values are determined with Latin hypercube sampling. This is done with the Community Atmosphere Model version 6 (CAM6), the atmospheric component of the Community Earth System Model version 2 (CESM2). We apply the PPE method to CESM2–CAM6 to understand climate sensitivity to atmospheric physics parameters. The initial simulations vary 45 parameters in the microphysics, convection, turbulence and aerosol schemes with 263 ensemble members. These atmospheric parameters are typically the most uncertain in many climate models. Control simulations and targeted simulations to understand climate forcing due to aerosols and fast climate feedbacks are analyzed. The use of various emulators is explored in the multi-dimensional space mapping input parameters to output metrics. Parameter impacts on various model outputs, such as radiation, cloud and aerosol properties, are evaluated. Machine learning is also used to probe optimal parameter values against observations. Our findings show that PPE is a valuable tool for climate uncertainty analysis. Furthermore, by varying many parameters simultaneously, we find that many different combinations of parameter values can produce results consistent with observations, and thus careful analysis of tuning is important. The CESM2–CAM6 PPE is publicly available and extensible to other configurations to address questions of other model processes in the atmosphere and other model components (e.g., coupling to the land surface).

Every teacher aspires to create the ideal lesson! You want to convey the knowledge and skills in the best possible way while also keeping learners motivated. In our design case, we focus on the complex skill of collaborative problem-solving (CPS). In today's complex world, the acquisition of CPS competencies is considered an important learning goal in education. However, there is limited knowledge on how to teach and assess CPS competencies. In addition to tackling these challenges, we search for new ways of interactive storytelling to implement in the learning materials. Our main design challenge was how to design a learning experience that encourages CPS. To address these challenges, we started in 2020 the project titled Supporting TEamwork in AMbient learning Spaces (STEAMS). In this project, we designed the EDUbox Teamwork, a four-hour learning activity for children between the ages of 10 to 14. In this paper, we describe the iterative process of designing the materials to learn about CPS (i.e., CPS as a learning goal) by doing CPS (i.e., CPS as a method), enhanced by interactive storytelling, for which the design-based research approach was used. The design team consisted of a diverse group of educational researchers, computer scientists, instructional graphical designers, digital storytellers, and teachers. Given the strong collaboration between a research group specialized in computer-supported collaborative learning and specialists in digital storytelling, our design case incorporated insights from both parties. The learning activity was piloted both in in-vivo and in-vitro contexts in collaboration with at least 400 students.

The Pacific Crest Trail (PCT) is a National Scenic Trail that extends approximately 2,653 miles from the border of California and Mexico to the border of Washington State and Canada. This study examined land management and hiker issues that day, overnight, and thru-hikers experience in California while navigating the PCT in order to inform land managers. This quantitative survey, completed through Qualtrics, was disseminated to thru-hikers who completed the trail between 2017 and 2021, and individuals who used the trail for shorter durations. Survey questions focused on technology, Trail Angels, rule enforcement by land management agencies, the permitting process by the Pacific Crest Trail Association (PCTA), hiker education, and hiker demographics. Descriptive statistics were calculated and analyzed. Results indicate that most hikers prefer articles on the PCTA website, Leave No Trace (LNT) website, and certifications to gain education about the trail. They also felt that personal contacts were the most effective way to gain pre-trip education. Almost all hikers use technology on the trail, such as navigation or informational apps, emergency calls, taking photos, and listening to videos or music. More thru-hikers rely on navigational apps than day/overnight users. Many hikers felt there should be more rangers in the backcountry but also felt that social enforcement of rules is effective. Regarding Trail Angels, thru-hikers felt they were important for transportation, food/water, and shelter. Managerial implications for public land managers included a need to develop ways to educate users. This can be done in-person, online, or through signage. Increasing the presence of rangers or volunteers on the trail was also recommended, as well as developing area or jurisdiction-specific apps for information and education about trail conditions or rules. Additional education of sustainable hiking behaviors may help mitigate potential negative impacts hikers may have on the environment. Land managers must continue to assess what is currently being done and reevaluate on an ongoing basis in order to preserve and maintain sustainable use of public lands.

Summary: Endocannabinoids, signaling through the cannabinoid CB1 receptor (CB1R), regulate several forms of neuronal plasticity. CB1Rs in the developing primary visual cortex (V1) play a key role in the maturation of inhibitory circuits. Although CB1Rs were originally thought to reside mainly on presynaptic axon terminals, several studies have highlighted an unexpected role for astrocytic CB1Rs in endocannabinoid mediated plasticity. Here, we investigate the impact of cell-type-specific removal of CB1Rs from interneurons or astrocytes on development of inhibitory synapses and network plasticity in mouse V1. We show that removing CB1Rs from astrocytes interferes with maturation of inhibitory synaptic transmission. In addition, it strongly reduces ocular dominance (OD) plasticity during the critical period. In contrast, removing interneuron CB1Rs leaves these processes intact. Our results reveal an unexpected role of astrocytic CB1Rs in critical period plasticity in V1 and highlight the involvement of glial cells in plasticity and synaptic maturation of sensory circuits.

PCR-based diagnostics has revealed the previously largely unknown Cryptosporidium transmission and infections in high-income countries. This study aimed to determine domestic and imported subtypes of Cryptosporidium species in Norway, evaluate their demographic distribution, and identify potential small outbreaks. Cryptosporidium-positive human faecal samples were obtained from six medical microbiology laboratories between February 2022 and January 2024, together with 22 Cryptosporidium-positive animal samples. Species and subtypes were identified by sequencing PCR products from gp60 and SSU rRNA genes. Most cryptosporidiosis cases occurred during late summer/early autumn, primarily in children and young adults. Of 550 human samples, 359 were successfully characterized molecularly (65%), revealing infection with 10 different Cryptosporidium species. C. parvum occurred in 245 (68%) human isolates with IIa and IId being major allele families, with distinct regional distribution patterns of common subtypes. A kindergarten outbreak with 5 cases was due to C. parvum IIaA14G1R1. C. mortiferum was identified in 33 (9.2%) human cases of which 24 were known to be of domestic origin, making it the second most common species in human autochthonous cases in Norway. All C. mortiferum isolates were of the same genotype; XIVaA20G2T1, including 13 cases from a suspected small outbreak in Trøndelag. C. hominis occurred in 68 typed cases (19%), but mostly in infections acquired abroad, with allele families Ib and If occurring most often. In conclusion, this study of recent Cryptosporidium spp. and subtypes in Norway, highlights the predominance of C. parvum and the emergence of C. mortiferum among autochthonous cases.

Hydro-pedotransfer functions (PTFs) relate easy-to-measure and readily available soil information to soil hydraulic properties (SHPs) for applications in a wide range of process-based and empirical models, thereby enabling the assessment of soil hydraulic effects on hydrological, biogeochemical, and ecological processes. At least more than 4 decades of research have been invested to derive such relationships. However, while models, methods, data storage capacity, and computational efficiency have advanced, there are fundamental concerns related to the scope and adequacy of current PTFs, particularly when applied to parameterise models used at the field scale and beyond. Most of the PTF development process has focused on refining and advancing the regression methods, while fundamental aspects have remained largely unconsidered. Most soil systems are not represented in PTFs, which have been built mostly for agricultural soils in temperate climates. Thus, existing PTFs largely ignore how parent material, vegetation, land use, and climate affect processes that shape SHPs. The PTFs used to parameterise the Richards–Richardson equation are mostly limited to predicting parameters of the van Genuchten–Mualem soil hydraulic functions, despite sufficient evidence demonstrating their shortcomings. Another fundamental issue relates to the diverging scales of derivation and application, whereby PTFs are derived based on laboratory measurements while often being applied at the field to regional scales. Scaling, modulation, and constraining strategies exist to alleviate some of these shortcomings in the mismatch between scales. These aspects are addressed here in a joint effort by the members of the International Soil Modelling Consortium (ISMC) Pedotransfer Functions Working Group with the aim of systematising PTF research and providing a roadmap guiding both PTF development and use. We close with a 10-point catalogue for funders and researchers to guide review processes and research.

Animal temperament refers to the inherent behavioural and emotional characteristics of an animal, influencing how it interacts with its environment. The selection of sheep for temperament can change the temperament traits of the selected line and improve the welfare and production (reproduction, growth, immunity) of those animals. To understand the genetics that underly variation in temperament in sheep, and how selection on temperament can affect other production traits, a genome-wide association study was carried out. Merino sheep from lines selected for traits of calm and nervous temperament, and a commercial population, on which the temperament traits had never been assessed, were used. Blood samples from the three populations were genotyped using an Illumina GGP Ovine 50 K Genotyping BeadChip. The calm and nervous populations in the selected lines presented as distinct genetic populations, and 2 729 of the 45 761 single nucleotide polymorphisms (SNPs) had significantly different proportions between the two lines. Of those 2 729 SNPs, 2 084 were also associated with temperament traits in the commercial population. A genomic annotation identified 81 candidate genes for temperament, nearly half of which are associated with disorders of social behaviour in humans. Five of those 81 candidate genes are related to production traits in sheep. Two genes were associated with personality disorders in humans and with production traits in sheep. We identified significant enrichment in genes involved in nervous system processes such as the regulation of systemic arterial blood pressure, ventricular myocyte action, multicellular organismal signalling, ion transmembrane transport, and calcium ion binding, suggesting that temperament is underpinned by variation in multiple biological systems. Our results contribute to understanding of the genetic basis of animal temperament which could be applied to the genetic evaluation of temperament in sheep and other farm animals.

Vinasse, a by-product of ethanol production, is generated at significant rates. While rich in nutrients such as calcium, magnesium, and potassium, its high solids, organic matter, acidity, and sulfate content pose challenges when disposed directly on soil, necessitating treatment. Anaerobic digestion is a viable solution, reducing organic pollution while recovering energy in the form of biogas, aligning with the biorefinery concept. Traditionally, sludge bed reactors and anaerobic contact reactors are utilized for vinasse processing, with sludge granulation being vital for treatment success. However, challenges such as sludge wash-out due to recalcitrant compounds, high solids concentration in the influent, low pH, salinity, and temperature hinder granule formation. Anaerobic membrane bioreactors (AnMBR) offer an alternative, simplifying treatment by integrating intensified pre- and post-treatment units. Due to complete sludge retention, AnMBRs achieve high COD removal efficiencies, yielding a suspended solids-free and largely disinfected effluent. Therefore, AnMBRs show promise for vinasse treatment, eliminating the need for sludge granulation and producing nutrient-rich effluent with minimal residual organics and suspended solids. In this study, an AnMBR equipped with an inside-out external crossflow ultrafiltration membrane was proposed for the treatment of vinasse. The AnMBR reached a COD removal efficiency of 95% ± 2.6% and produced 0.3 CH4 L. g COD removed-1 working at organic loading rates of 8 g COD. L-1 d-1 and membrane fluxes of 10 LMH. At organic loading rates of 10 g COD. L-1 d-1 and fluxes of 12 and 14 LMH, the COD removal efficiency decreased to 77% ± 11% and 73% ± 7.9%, respectively. The AnMBR technology represents an innovation for wastewater treatment, however, more research using the cross-flow configuration and different types of effluents is needed. Literature studies that address the treatment of sugar beet or sugarcane vinasse using AnMBR are still scarce. This study explored the potentials of AnMBR technology for vinasse treatment and contributes to the dissemination of this technology, opening new possibilities for vinasse processing.

Vinasse is a by-product of sugarcane processing which is often used in fertigation; however, the direct use of vinasse harms the environment and reduces soil productivity due to its physicochemical properties. Anaerobic digestion (AD) offers an alternative to mitigate part of the negative effects. Anaerobic high-rate reactors, which mainly rely on sludge granulation, are mostly used in AD of vinasse wastewater. However, the composition of vinasse such as high concentration of solids and organic matter, high salinity, low pH, and high concentrations of sulfate, affect granule formation, leading to sludge washout. Anaerobic membrane bioreactors (AnMBR) present an alternative for vinasse treatment, eliminating the need for sludge granulation and producing a nutrient-rich effluent with minimal residual organics and no suspended solids. Research on sugarcane vinasse treatment using AnMBRs is limited. Most studies have employed submerged internal membrane modules, highlighting the need for further research with different reactor configurations to enhance process performance. In this study, an AnMBR equipped with an external inside-out crossflow ultrafiltration membrane was compared to an upflow anaerobic sludge blanket (UASB) reactor for the treatment of sugarcane vinasse. At a volumetric organic loading rate of up to 6 g COD. L-1.d-1, the UASB reactor reached 75% ± 7% of COD removal efficiency whereas the AnMBR generated a solids-free effluent and reached 88% ± 2% of COD removal efficiency. Microorganisms such as Clostridia, Bacteroidia, Mesotaga, Syner-01, Dehalococcoidia, Bacteroidia-DMER64, and Methanolinea were found as the most abundant. The results highlight the AnMBR potential as an effective alternative for treating sugarcane vinasse while overcoming the challenges posed by unsatisfactory sludge granulation.

Høyere yrkesfaglig utdanning har i de senere årene fått oppmerksomhet med blant annet fokus på Fagskolen. Høyskolen for Yrkesfag (HØFY) ble etablert i 2019, og i 2020 ble det første kullet bachelor i byggeplassledelse tatt opp. Høsten 2023 har totalt 235 studenter gjennomført eller gjennomfører studiet ved HØFY. Det er viktig for HØFY som utdanningsinstitusjon å få kjennskap til sine studenter og deres erfaringer og kompetanse. Derfor ble det etablert en spørreundersøkelse som er denne artikkelens empiriske grunnlag. Problemstillingen er todelt, den første er mot hvilke ressurser og kompetanse studentene besitter, og den andre delen retter søkelys på hvilke innsatsfaktorer disse kvalifikasjonene kan være i konstruksjonen av et tredje læringsrom, altså grensesnittet «skole – arbeidsliv». Resultatene fra spørreundersøkelsene dokumenterer at studentene har en rik arbeidserfaring, som lærling, fagarbeider og med ulike lederoppgaver, i tillegg solid formell utdanning. Den andre delen av Problemstillingen diskuterer hvordan og hvorfor studentenes erfaringer og kompetanse kan komme i spill under konstruksjonen av et hybrid læringsrom som en hensiktsmessig læringsarena for denne type studenter.

Background and purpose: Patients with cardiac implantable electronic devices (CIED patients) are often ineligible for online magnetic resonance-guided radiotherapy (MRgRT), most likely due to the absence of established guidelines. Existing radiotherapy (RT) and magnetic resonance imaging (MRI) guidelines offer an opportunity to construct MRgRT protocols, promoting equitable access. Our objective was to present such a workflow, share multi-institutional experiences treating CIED patients with MRgRT on a 1.5 T magnetic resonance-linear accelerator (MR-linac), and investigate geometric accuracy and electrocardiogram (ECG) monitoring for thoracic treatment. Materials and methods: A risk analysis identified strategies for safe MRgRT for CIED patients. At three institutions, 21 pelvic and abdominal patients were treated. Patient records were analyzed for adverse events. Geometric accuracy was investigated using B0-mapping with a phantom simulating moving lung and cardiac lesions near a CIED. Volunteer measurements evaluated the effects of patient positioning and MRI sequences on ECG signal distortion. Results: MRI and RT workflows were adaptable to MRgRT. No adverse events were recorded. B0-maps showed a maximum mean difference between static and dynamic phantom configurations of 0.1 mm, increasing to 0.4 mm distortion in the presence of a CIED. ECG readings exhibited severe distortions during scanning, hampering heart rhythm detection for most MRI sequences. Conclusions: CIED patients can safely undergo treatment on a 1.5 T MR-linac following RT and MRI guidelines. For targets near CIEDs, a B0-mapping procedure was considered accurate enough to determine MRgRT eligibility. Pulse oximetry is recommended for cardiac monitoring during MRI scanning due to ECG signal distortion.

Process-based crop models have faced rapid development over the last years, and many modelling platforms are now available and can be used in a wide range of conditions. Whilst the selection of a model should be suited to the purpose of its application, very few studies focused on the impact of choosing different model structures and data details on the simulation outputs. One important aspect is the soil water dynamics, which can be simulated at different levels of details in terms of data and approaches. In this study, we investigated the impact of model structure and data detail on simulations of sugarcane growth and irrigation scheduling. Three different soil water routines (Standalone, Tipping-Bucket, SWAP) were coupled with the SAMUCA model and calibrated with a comprehensive field experiment dataset. We also tested the influence of using simplified homogeneous (SL) and detailed (DL) soil profile information in model performance. The model framework was evaluated against independent field experiments across Brazil and used to simulate long-term sugarcane growth and irrigation scheduling. After calibration, the SWAP-DL showed the highest accuracy in soil moisture predictions, with a 6 % error (RRMSE), but the difference from TippingBucket-DL was small (8 %). While the performance of stalk dry mass, LAI and water-use efficiency simulations were within the range found in literature, comprehensive field experiments showing significant impacts of drought on sugarcane growth are still lacking for a more rigorous evaluation. Both SWAP and tipping-bucket approaches showed higher robustness to soil data detail as compared to the Standalone method, which should be avoided when soil water is critical for sugarcane growth. The use of tipping-bucket method may still be preferred when the research goal is focused on crop growth and soil parameters are limited. SWAP-SAMUCA may provide an extended ability to represent agrohydrological processes in sugarcane plantations and process understanding.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often >2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

We introduce a new illusory color phenomenon. The illusion is evoked by two alternating displays comprising various colored disks. Although the colors in the alternating displays are the same, the color appearance of the two displays are quite different. We suggest that apparent motion of the disks modulates the color percepts.

This paper highlights the evolution and impact of the SWAP model (Soil – Water – Atmosphere – Plant), which was initiated by R.A. Feddes and colleagues fifty years ago, in 1974. Since then, the SWAP model has played a crucial role in the advancement of agrohydrology. This paper highlights some major advances that have been made, especially focussing on the last fifteen years. The domain of the SWAP model deals with the simulation of the soil water balance in both unsaturated and saturated conditions. The model solves the Richards equation using the water retention and hydraulic conductivity functions as described by the Van Genuchten – Mualem equations. Bimodal extensions of the Van Genuchten - Mualem relationships have been implemented, as well as modifications near saturation and addressing hysteresis. An important sink term in the Richards equation is root water uptake. Crop development plays an important role in a robust simulation of root water uptake. That is why a link has been made with the dynamic crop growth model WOFOST. Instead of using a prescribed crop development, a distinction between potential and actual crop development is calculated by reducing the potential photosynthesis as a result of water or oxygen stress. Since the early days of SWAP, empirical and macroscopic concepts have been used to simulate root water uptake. Recently two process-based concepts of root water uptake and oxygen stress have also been implemented. Another important sink-source term in the Richards equation is the interaction with artificial drains. In SWAP, drainage can be simulated by either using prescribed or simulated drain heads and simulation of controlled drainage with subirrigation is possible. Finally, we briefly elaborate on three studies using SWAP: water stresses in agriculture in the Netherlands, regional water productivity in China, and controlled drainage with subirrigation. We finish discussing promising developments for the near future.

Warm rain collision-coalescence has been persistently difficult to parameterize in bulk microphysics schemes. We use a flexible bulk microphysics scheme with bin scheme process parameterizations, called AMP, to investigate reasons for the difficulty. AMP is configured in a variety of ways to mimic bulk schemes and is compared to simulations with the bin scheme upon which AMP is built. We find that an important limitation in traditional bulk schemes is the use of separate cloud and rain categories. When the drop size distribution is instead represented by a continuous distribution, the simulation of cloud-to-rain conversion is substantially improved. We also find large sensitivity to the threshold size to distinguish cloud and rain in traditional schemes; substantial improvement is found by decreasing the threshold from 40 to 25 μm. Neither the use of an assumed functional form for the size distribution nor the choice of predicted distribution moments has a large impact on the ability of AMP to simulate rain production. When predicting four total moments of the liquid drop size distribution, either with a traditional two-category, two-moment scheme with a reduced size threshold, or a four-moment single-category scheme, errors in the evolution of mass and the cloud size distribution are similar, but the single-category scheme has a substantially better representation of the rain size distribution. Optimal moment combinations for the single-category approach are investigated and appear to be linked more to the information content they provide for constraining the size distributions than to their correlation with collision-coalescence rates.