Large Complex Research Articles

Returns from rare coins: a machine learning approach

Abstract Despite the existence of several studies on collectibles, the rare coin market is still underexplored. This paper examines this market with a sample of 5553 Spanish columnarios (1732–1772) auctioned from 1992 to 2021, investigating the key factors influencing auction prices using a dataset with an extensive number of covariates. Traditional hedonic models face challenges with large datasets, including multicollinearity, overfitting, and parameter complexity, which compromise clear and reliable interpretation. To address these limitations, this study employs the cross-fit partialing-out LASSO regression to select key explanatory variables, resulting in unbiased estimates and insights for investors and researchers. An interrupted time series analysis is subsequently conducted to compare indices derived from the traditional and LASSO hedonic methods. Findings confirm that LASSO approach outperforms the traditional hedonic regression method in terms of estimation accuracy.

ОЦЕНКА ЭФФЕКТИВНОСТИ ВАКЦИН И ДЕЗИНФЕКТАНТОВ ПРОТИВ КЛОСТРИДИОЗА КОРОВ НА МОЛОЧНЫХ КОМПЛЕКСАХ РЕСПУБЛИКИ БАШКОРТОСТАН

The purpose of the study is to evaluate the preventive effectiveness of the use of modern veterinary vaccines (One Shot Ultra 8, TOXIPRA Plus, Koglavax and Pastanarm 8) and the disinfectant Forbicida in comparison with hydrogen peroxide against clostridiosis of dairy cows, carried out in conditions of large dairy complexes of the Republic of Bashkortostan. Analyzes of biomaterial (internal organs and blood serum) of cows were carried out at the testing center of the State Budgetary Institution “Bashkir Research and Production Veterinary Laboratory” in compliance with regulated methods and in accordance with approved regulatory documents – international standards (GOST) and technical specifications (TU). Based on the laboratory tests carried out, we can conclude that without objective identification of the species of anaerobic bacteria clostridia, uncontrolled vaccination of livestock does not provide the necessary level of protection of the body of dairy cattle from this disease. According to the obtained microscopic studies of pathological materials, the most common cultures of clostridia cells are the species of perfringens (C. perfringens) and chauvoei (C. chauvoei), the latter of which is the causative agent of livestock emkara. In this regard, to maintain the required level of specific immunity protection of cows, monthly monitoring of antibodies to toxins remains, the level of which should be at least 40 % inhibition. However, the high effectiveness of specific prevention of clostridia is not achieved by any of the listed vaccines, which requires mandatory monitoring of the level of inhibition of antibodies in blood serum to identified types of clostridia and the introduction of strict sanitary treatment of livestock areas with disinfectant solutions. The use of a 10 % solution of Forbicida or 6 % hydrogen peroxide with an exposure of 24 and 3 hours, respectively, ensures 100 % death of pathogenic bacteria of the 3rd–4th group.

Vacuolar Sts1 Degradation-Induced Cytoplasmic Proteasome Translocation Restores Cell Proliferation.

The proteasome is a large multicatalytic complex conserved across eukaryotes that regulates multiple cellular processes through the degradation of ubiquitinated proteins. The proteasome is predominantly localized to the nucleus in proliferating cells and translocates to the cytoplasm in the stationary phase. Sts1 reportedly plays a vital role in the nuclear import of the proteasome during proliferation in yeast Saccharomyces cerevisiae. However, the mechanisms underlying cytoplasmic translocation of the proteasome in the stationary phase remain unknown. Here, we showed that the ubiquitin ligase Hul5 promotes vacuolar sequestration of Sts1 in a catalytic activity-dependent manner and thus suppresses the nuclear import of the proteasome during the stationary phase. We further demonstrated that cytoplasmic translocation of the proteasome plays a vital role in the clearance of ubiquitinated protein aggregates, mitochondrial quality control, and resuming proliferation from cellular quiescence. Our results provide insights into the mechanisms and significance of the cytoplasmic localization of proteasomes in cellular quiescence.

Integrating AI and climate change scenarios for multi-risk assessment in the coastal municipalities of the Veneto region.

Global climate is experiencing exceptional warming, leading to a rise in extreme events worldwide. Coastal regions are particularly vulnerable to climate change (CC), due to dense populations, interconnected economies, and fragile ecosystems. These areas face escalating risks as CC intensifies the severity and frequency of extreme weather phenomena, like heavy precipitation, sea-level rise (SLR), storm surges. Integrated approaches are crucial to assess the combined impacts of atmospheric and marine hazards at the land-sea interface. Machine Learning (ML) offer innovative solutions to analyse multi-risk events, leveraging large and heterogeneous datasets and modelling complex, non-linear interactions. This study introduces a two-tier ML approach to estimate risks associated with extreme weather events for the Veneto coastal municipalities under current and future scenarios. The model, tested and validated with present-day data, showed satisfactory performance (error margin ∼20%). The model was applied to mid-term (until 2045) and long-term (until 2100) periods under different CC scenarios, represented by various Representative Concentration Pathways (RCP). Mid-term analysis reveals an increasing risk trend, driven by SLR under RCP8.5, underscoring the significance of considering non-linear interactions between multiple marine and atmospheric hazards. Long-term analysis highlights how future risks depend mainly on precipitation and SLR across the analysed CC scenarios (RCP2.6/4.5/8.5). Results indicate a gradual increase in the expected annual risk trend, with RCP8.5 scenario showing the most severe outcomes. By 2100, the risks under RCP8.5 are projected to be ten times higher than those observed during the historical period, highlighting the importance of developing effective strategies to address these challenges.

Metastatic Hobnail Papillary Thyroid Carcinoma Initially Diagnosed by Pleural Effusion: Case Report of a Rare and Intriguing Entity.

Hobnail papillary thyroid carcinoma (HNPTC) is an unusual and aggressive variant of PTC. Malignant pleural effusion secondary to thyroid carcinoma is a rare event reported in less than 1% of cases. Herein we present a case of metastatic HNPTC initially diagnosed by pleural effusion cytology, with a very poor outcome. A 42-year-old male with no previous cancer history, presented with an anterior neck mass growing for the past year. A computed tomography (CT) scan revealed a large complex cystic lesion with mass effect on the anterior thyroid gland, along with multiple neck and mediastinal necrotic lymph nodes, suspicion for metastasis. CT of the thorax showed lung nodules and a large left pleural effusion. Fluid was drained and sent for cytologic examination which revealed malignant cells predominantly in a micropapillary pattern with apically placed, bulged, "hobnail-like" appearance; intranuclear pseudo-inclusions or chromatin clearing was not seen. Based on cytomorphologic findings and immunohistochemical results (CK7 and PAX-8 positive; TTF-1, Napsin-A, and mesothelial markers negative), final diagnosis of HNPTC metastatic to pleural fluid was made. Fine-needle aspiration of neck mass showed similar cytomorphologic findings, confirming a thyroid origin. However, the patient experienced complications, rapid deterioration and died 6 months after diagnosis. The intersection of clinical-radiologic findings, cytology, and immunohistochemistry guided the identification of this rare variant of PTC as the origin of the malignant pleural effusion. We believe this case provides a valuable insight into the complexities involved in the diagnosis of thyroid carcinoma and emphasizes the significance of proper identification of rare variants.

P-1858. Exploring the Role of Fatty acid synthase (FASN) Inhibition in Interferon Gamma Mediated Killing of Histoplasma capsulatum

Abstract Background Histoplasma capsulatum (Hc) is the leading cause of fungal respiratory infections in the US. Most cases are mild but 20% require hospitalization. Immunosuppression is a major risk factor for disseminated histoplasmosis. The cytokine Interferon gamma (IFN)-γ is crucial for host resistance to Hc. The absence of IFN-γ or its failure to signal affects the host immune response. Activated CD4+ T cells release IFN-γ to arm macrophages(MΦ) to kill intracellular yeasts. Immunometabolism is a key element in the function of MΦ and fatty acid synthase (FASN) regulates inflammatory responses by these cells. FASN is a large multi-enzyme complex comprised of 6 separate enzymatic grooves that work together to produce 16-carbon chain saturated fatty acid (FA), palmitate, from acetyl-coenzyme A (CoA) and malonyl-CoA(Figure 1). The influence of FASN in the IFN-γ-mediated activation of MΦ remains unclear. Key inhibitor targets in FASN complex Methods Figure 1 shows key inhibitor targets in FASN complex. Bone marrow derived Mφ were used in all experiments with a 2 to 1 yeast to Mφ ratio. IFN-γ induced killing of Hc in mouse Mφ require 48h. We used the tetrazolium salt XTT to assess the Hc viability as this correlates with the colony counts. Controls (Hc in Mφ) are set to 100 %. Toxicity of each inhibitor to Hc and Mφ was studied first. Mφ were treated with IFN-γ 4hrs before infection and then treated with graded amounts of FASN inhibitors C 75 (inhibits ketoacyl synthase), orlistat (inhibits thioesterase), and TVB-3166 or GSK2194069 (both inhibit ketoacyl synthase) 2hrs before infection with 2x Hc for 48hrs. Intracellular yeast survival at 48hrs was assessed. Effect of FASN inhibitors on IFN- γ mediated killing of Hc at 48 hrs. n= 3-10 , mean ±SEM Results Pretreatment with the FASN inhibitor C75 reversed the killing activity of IFN- γ. Neither orlistat or inhibitors of ketoacyl reductase modified the impact of IFN-γ. (Figure 2) Conclusion The FASN inhibitor C75 reversed the activity of IFN-γ in killing Hc. These results suggest that cholesterol synthesis may be involved in the action of IFN- γ. Disclosures All Authors: No reported disclosures

Drill Pattern Optimisation for Large Complex Blasts to Improve Fragmentation and Dig Efficiency

Abstract At large-scale open-pit metallic mines, drill-and-blast designs can reach over 1,000 drill holes per blast. A critical input to the design of a blast is the location of sensitive zones where ground vibration, air overpressure or flyrock needs to be constrained. The other critical input is the hardness profile of the ground. Often, the hardness across such large blasts varies significantly from soft to extra hard. Traditional approaches for pattern design use constant distance (burden and spacing) between the production drill holes and vary the explosive product strength and amount in each hole to account for variation in hardness and to adhere to blast constraints. Although this approach is operationally easier to execute, it is challenging to meet fragmentation and diggability objectives. To better address these objectives, this work provides a nonlinear mathematical model for optimising drill hole locations in conjunction with explosive amounts. The model optimises the design using a three-stage methodology. In the first stage, a novel heuristic method is used to perform local optimisation to determine the number of holes. In the second stage, the precise hole locations are determined, and in the third stage the energy intensity in each hole is optimised. In a study of 10 blasts from a Pilbara iron ore mine, for the dig efficiency objective, results indicate that variable designs achieve $$\sim $$ ∼ 2% better dig efficiency, with $$\sim $$ ∼ 11% fewer holes. For the fragmentation objective, variable designs achieve $$\sim $$ ∼ 9% better adherence to the target mean particle size, with $$\sim $$ ∼ 5% less standard deviation and $$\sim $$ ∼ 13% fewer holes.

How to correct Ehrenfest nonadiabatic dynamics in open quantum systems: Ehrenfest plus random force (E + σ) dynamics.

One key challenge in the study of nonadiabatic dynamics in open quantum systems is to balance computational efficiency and accuracy. Although Ehrenfest dynamics (ED) is computationally efficient and well-suited for large complex systems, ED often yields inaccurate results. To address these limitations, we improve the accuracy of the traditional ED by adding a random force (E + σ). In this work, the construction of random forces is considered in Markovian and non-Markovian scenarios, and we ensure the dynamics satisfy the detailed balance in both scenarios. By comparing our E + σ with existing methods such as the electronic friction model and surface hopping, we furthermore validate its reliability. In addition, the E + σ model still retains the high efficiency of ED and does not incur much additional computation. We believe that this method provides an alternative to accurately describe the mixed quantum-classical dynamics in open quantum systems, particularly for large complex systems.

SMARCA4 deficiency in small cell lung cancer: A case report and narrative review of the literature

SWItch/Sucrose Non-Fermentable (SWI/SNF) is a large protein complex with a central role in chromatin remodeling and genome transcription. The catalytic subunits of the SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2 (SWI/SNF SMARCA2; also called BRM) and SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4; also called BRG1) are encoded by the SMARCA2 and SMARCA4 genes, respectively, and are mutually exclusive. Loss of either SMARCA2 and/or SMARCA4 has been previously reported in several types of malignant solid tumors of the gastrointestinal and genitourinary tract. So far, their absence in non-small cell lung cancer has been observed in a series of studies involving primary tumors and cell lines, where it is associated with loss of differentiation and heightened tumorigenic potential leading to an unfavorable prognosis. SMARCA2 and SMARCA4 deficiency is frequent in solid predominant adenocarcinomas and tumors with low levels of bronchial epithelial markers, including thyroid transcription factor 1. A rare case of SMARCA4 deficiency in small cell lung cancer is described. A 57-year-old male patient, with no medical history of past illness, was admitted to our center for the investigation and management of a space-occupying lesion in the right upper lung lobe with tracheal and mediastinal infiltration. Biopsy of a lymph node in the right supraclavicular region was diagnostic for small cell lung cancer with regional loss of SMARCA4. The patient demonstrated progressive respiratory failure and clinical deterioration and eventually deceased despite intubation and transfer to the intensive care unit. This case indicates that SMARCA4-deficient small cell lung cancer may present with an aggressively deteriorating phenotype with poor outcomes for the patie

Possibilities and limitations of new radiocarbon dating for the Maucallacta site, dep. Arequipa, Peru

Abstract With the development of radiocarbon dating methods in the last decade, the Andean archaeological community has successfully leaned into the problem of the chronology of the expansion of the Inca State. While this chronology was based on ethnohistorical accounts (Rowe 1945), it has been possible to verify its foundations precisely in the last decade. The results from the Maucallacta region are part of these discussions and are intended to add new data from the Inca province of Kuntisuyu, which was neglected in this debate until now. The project encompasses archaeological investigations near the snow-covered volcano Coropuna, frequently mentioned by chroniclers of the 16th and 17th centuries as an oracle worshiped since pre-Inca times. This includes a large complex known as Maucallacta-Pampacolca, located approximately 170 km northwest of Arequipa in the southern highlands of Peru, within the District of Pampacolca, Province of Castilla, Department of Arequipa (LS; 3750 m asl). Due to its location, it holds a unique relationship with the Coropuna landscape. The site is a vast administrative center featuring over three hundred stone buildings, tombs, and ceremonial structures. Among them, the most important is the large ceremonial platform with ushnu and the dumps deposited beneath it. The analysis of ceramics and animal bones, combined with stratigraphic analysis and the results of new calibrations and interpretations of radiocarbon dates, provides a comprehensive picture of the formation and use of ceremonial dumps at the site, making them one of the most thoroughly examined collections in this regard.

Alterations in Lipid Saturation Trigger Remodeling of the Outer Mitochondrial Membrane.

Mitochondrial-derived compartments are multilamellar structures that sequester protein and lipids of the outer mitochondrial membrane in response to metabolic and membrane perturbations, but it is largely unknown how membrane fluidity influences this pathway.Increased levels of unsaturated phospholipids may disrupt the TOM complex, a large multi-subunit complex on the outer mitochondrial membrane, to promote the formation of mitochondrial-derived compartments, while increased levels of saturated phospholipids inhibits formation of mitochondrial-derived compartments.These findings reveal a link between phospholipid composition and protein stress in driving mitochondrial-derived compartment biogenesis, and thus mitochondrial quality control.

P0640 Development and characterization of LQ080, a novel extended half-life bispecific TL1A/IL-23 p19 single domain antibody for the treatment of IBD

Abstract Background Despite the effectiveness of current anti-TL1A treatments, unmet needs remain for effective therapeutics for IBD. Therapies simultaneously neutralizing TL1A and IL-23 might be better choices owing to their synergistic anti-inflammatory effects in the pathogenesis of IBD. Methods TL1A and IL-23 single domain antibodies (sdAbs) were selected from immunized sdAb Phage display libraries. A human whole blood-based assay measuring IFNγ secretion was used to assess functional blockade of TL1A. Mouse splenocytes based assay measuring mouse IL-17 release was used to evaluate functional blockade of IL-23. Dextran Sulfate Sodium (DSS) induced mouse bowel inflammatory model was used to judge the in vivo effect of anti-TL1A antibodies. Synergistic anti-inflammatory effect was evaluated in mouse dermatitis model. Half-life extension was measured via pharmacokinetic analysis in non-human primate (NHP) given a single bolus of LQ080 by subcutaneous administration. Results The TL1A sdAb, which binds to both soluble and membrane-bound TL1A in a pH dependent pattern, potently blocked TL1A/DR3 while leaving the TL1A/DcR3 binding undisturbed and illustrated better IFNγ release in human whole blood induced by TL1A than RVT-3101 and PRA023. In DSS model, the TL1A sdAb also demonstrated better anti-inflammation effect than RVT-3101. The TL1A/IL-23 p19 biparatropic sdAb, LQ080, showed better IFNγ secretion inhibition than RVT-3101 and PRA023, and better inhibition of mouse IL-17 induction than Risankizumab and Guselkumab. Synergistic effects were found using LQ080 in both IFNγ release inhibition in human PBMCs induced by IL-23 and TL1A and in the mouse dermatitis model. The half-life of LQ080 significantly extended of 2-3 folds in non-human primate (NHP) compared to that of RVT-3101. Besides, LQ080 did not form large immune complex in vitro when mixed with TL1A and IL-23. Moreover, LQ080 did not stimulate the release of pro-inflammatory cytokines in the cytokines release assay. Conclusion The TL1A sdAb demonstrated better bioactivity than RVT-3101 and PRA023. LQ080, a TL1A/IL-23 p19 biparatropic sdAb, illustrated synergistic anti-inflammation effect both in vitro and iv vivo for its simultaneous neutralization of TL1A/DR3 and IL-23/IL-23R pathways, which would greatly improve the clinical results of IBD patients. The pH dependent TL1A binding makes LQ080 very different from other anti-TL1A mAbs. LQ080 demonstrated extended half-life in NHP making infrequent dosing possible for IBD treatment. No large immune complex formation when mixed with TL1A and IL-23 would make LQ080 safer when administrated by SC route. Overall, LQ080 is a promising TL1A/IL-23 p19 sdAb for IBD treatment.

Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.

Glutamine synthetase (GS) is a ubiquitous enzyme central to nitrogen metabolism, catalyzing the ATP-dependent formation of glutamine from glutamate and ammonia. Positioned at the intersection of nitrogen metabolism with carbon metabolism, the activity of GS is subject to sophisticated regulation. While the intricate regulatory pathways that govern Escherichia coli GS were established long ago, recent work has demonstrated that homologues are controlled by multiple distinct regulatory patterns, such as the metabolite induced oligomeric state formation in archaeal GS by 2-oxoglutarate. Such work was enabled in large part by advances in cryo-electron microscopy (cryoEM) that allowed greater structural access to this large enzyme complex, such as assessment of the large heterogeneous oligomeric states of GS and protein-interactor-GS complexes. This perspective highlights recent advances in understanding GS regulation, focusing on the dynamic interplay between its oligomeric state, metabolite binding, and protein interactors. These interactions modulate GS activity, influencing cellular processes such as nitrogen assimilation, carbon metabolism, and stress responses. Furthermore, we explore the emerging concept of GS "moonlighting" functions, revealing its roles in palmitoylation, cell cycle regulation, and ion channel modulation. These diverse functions highlight a newfound versatility of GS beyond its primary catalytic role and suggest complex roles in health and disease that warrant further study.

Continuity Amid Commercial Buildings in Yeonnam-dong, Seoul

This study tracks changes in commercial buildings in Yeonnam-dong that have undergone commercial transformation, examining these shifts within the context of urban organization and their relationships with economic and socio-cultural flows. It also analyzes the architectural elements that reflect the placeness characteristics of an area. On-site surveys were conducted to assess the continuity and discontinuity in the characteristics of 62 renovated and 40 newly constructed buildings. Additionally, shifts in social perceptions regarding physical changes were explored through an analysis of commercial districts and interviews with visitors, store owners, and architects. Yeonnam-dong has a distinct physical environment, as well as economic, social, and cultural characteristics that distinguish it from mainstream areas, such as large apartment complexes and typical commercial zones. The area, with its winding alleyways from the pre-modern period and low-rise housing—marginalized from large-scale development—evoked nostalgia and created a distinctive sense of authenticity or placeness, which was further enhanced by the presence of exotic restaurants, cafés, ateliers, and creative activities of early gentrifiers. However, rapid commercialization has led to the displacement of these early gentrifiers, an influx of new investments and construction, and shifts in commercial flows. Consequently, the area’s authenticity has become diluted, and visitors’ perceptions of it have changed. Despite this, architectural elements observed in renovated buildings are preserved and incorporated into newly constructed ones. Features such as semi-basements, exterior straight stairs, and brick façades continue to reflect the locality. Detached and multi-household homes from the 1960s to the 1990s have evolved into a new hybrid commercial–residential form designed for commercial purposes. This is a response to small plot sizes in Korean residential areas and reflects the current economic and cultural demands of commercial gentrification. The urban and architectural characteristics of this area are not only a unique physical environment but also hold socio-cultural significance as ordinary heritage. Therefore, this study proposes institutional measures to preserve urban and architectural continuity while controlling the ongoing commercialization.

TCTEX1D2 is essential for sperm flagellum formation in mice

Flagella and cilia are widely conserved motile structures, in mammalian, sperm possess flagella. Large protein complexes called dynein, including cytoplasmic dynein 2 and axonemal dynein, play a role in the formation of cilia and flagella. The function of each subunit component of dynein complexes in sperm flagellum formation remains unclear. One such subunit is TCTEX1D2. Co-immunoprecipitation studies showed that TCTEX1D2 interacted with cytoplasmic dynein 2 subunits WDR34, WDR60, and DYNLT1 in the testes. Furthermore, TCTEX1D2 also interacted with WDR63 and WDR78, subunits of inner dynein arm, which is axonemal dynein. Tctex1d2−/− mice generated in this study exhibited male infertility due to flagellar dysplasia, and the axonemal structures were disrupted inside the flagella. Further, the localization of cytoplasmic dynein 2 subunits was abnormal in in Tctex1d2−/− mice. In contrast, the motile cilia of Tctex1d2−/− mice were normal. Overall, we revealed that TCTEX1D2 is important for the assembly of cytoplasmic dynein 2 and inner dynein arm and functions in two distinct dynein complexes during mouse sperm flagellum formation. This is only in sperm flagellum formation, not in cilia formation.

β-Diketonate Coordination: Vibrational Properties, Electronic Structure, Molecular Topology, and Intramolecular Interactions. Beryllium(II), Copper(II), and Lead(II) as Study Cases.

Nine metal complexes formed by three symmetric β-diketonates (viz., acetylacetonate (acac), 1,1,1,3,3,3-hexafluoro-acetylacetonate (hfac), and 2,2,6,6-tetramethylheptane-3,5-dionate (tmhd)) and three metal ions (with three different coordination geometries, viz., BeII - tetrahedral, CuII - square planar, and PbII - "swing" square pyramidal) were investigated. The study combines structural analyses, vibrational spectroscopic techniques, and quantum chemical calculations with the aim of bridging crystal structure, electronic structure, molecular topology, and far-infrared (FIR) spectroscopic characteristics. The effect of intramolecular interactions on the structural, electronic, and spectroscopic features is the center of this study. The crystal structure of Be(tmhd)2 is also reported and discussed for the first time. A complete review of the experimental IR spectra is offered; discrepancies in the assignments of some peaks are revealed among the published works. Anharmonic effects were considered for acac complexes; however, they were negligible for the FIR modes. A systematic comparison between computed and experimentally measured data allowed us to design an inexpensive, yet efficient computational protocol to investigate large polynuclear complexes.

Probing Biomolecular Interactions with Paramagnetic Nuclear Magnetic Resonance Spectroscopy.

Recent advances in computational methods like AlphaFold have transformed structural biology, enabling accurate modeling of protein complexes and driving applications in drug discovery and protein engineering. However, predicting the structure of systems involving weak, transient, or dynamic interactions, or of complexes with disordered regions, remains challenging. Nuclear Magnetic Resonance (NMR) spectroscopy offers atomic-level insights into biomolecular complexes, even in weakly interacting and dynamic systems. Paramagnetic NMR, in particular, provides long-range structural restraints, easily exceeding distances over 25 Å, making it ideal for studying large protein complexes. Advances in chemical tools for introducing paramagnetic tags into proteins, combined with progress in electron paramagnetic resonance (EPR) spectroscopy, have enhanced the method's utility. This perspective article discusses paramagnetic NMR approaches for analyzing biomolecular complexes in solution and in the solid state, emphasizing quantities like pseudocontact shifts, residual dipolar couplings, and paramagnetic relaxation enhancements. Additionally, dynamic nuclear polarization offers a promising method to amplify NMR signals of large complexes, even in complex environments. The integration of AlphaFold protein structure prediction with paramagnetic NMR holds great potential for advancing our understanding of biomolecular interactions.

Investigation of stakeholder perceptions of the wheelchair service delivery process

Introduction: The wheelchair service delivery process (SDP) is a large complex system and therefore has many potential points of failure; determining priorities for improvement is challenging. The complexities introduce several barriers to accessing and maintaining wheelchairs for individuals with mobility impairments. Given the breadth and depth of the barriers, it is important to know in which areas to focus future policy reform efforts. Purpose:The purpose is to explore the perceptions of stakeholders regarding the performance of the wheelchair SDP in the United States and guide future policy reforms. Methods: A cross-sectional, observational, online questionnaire was deployed. Questions were positive statements regarding the wheelchair SDP and participants rated their agreement with the statements on a standard six-point Likert scale. A snowball sampling strategy was used and consisted of emailing 42 organisations representing 5 stakeholder groups: (1) consumers/caregivers; (2) clinicians; (3) manufacturers; (4) payers; and (5) suppliers. Results: 1,052 responses were collected: 41% clinicians, 30% suppliers, 24% consumers/caregivers, 3% manufacturers, 2% payers. Stakeholders view the wheelchair SDP as not performing well. Less than 18% of all responses indicate a positive perception. Funding and procurement was viewed in the least positive light, with 5% positive responses. Follow-up, maintenance, and repair was the second least positive component with 9% positive responses. Fitting, training, and delivery was viewed most positively with over 42% positive responses. Conclusion: The wheelchair SDP is not viewed as performing well by its stakeholders. Funding, procurement, maintenance, and repairs are viewed particularly negatively, representing opportunities for focused system reform efforts.

Trees shape the soil microbiome of a temperate agrosilvopastoral and syntropic agroforestry system

Agroforestry systems are multifunctional land-use systems that promote soil life. Despite their large potential spatio-temporal complexity, the majority of studies that investigated soil organisms in temperate cropland agroforestry systems focused on rather non-complex systems. Here, we investigated the topsoil and subsoil microbiome of two complex and innovative alley cropping systems: an agrosilvopastoral system combining poplar trees, crops, and livestock and a syntropic agroforestry system combining 35 tree and shrub species with forage crops. Increasing soil depth resulted in a decline of bacterial and fungal richness and a community shift towards oligotrophic taxa in both agroforestry systems, which we attribute to resource-deprived conditions in subsoil. At each soil depth, the microbiome of the tree rows was compositionally distinct from the crop rows. We detected a shift towards beneficial microorganisms as well as a decline in putative phytopathogens under the trees as compared to the crop rows. Finally, based on our results on community dissimilarity, we found that compared to an open cropland without trees, spatial heterogeneity introduced by the tree rows in the agrosilvopastoral system translated into a compositionally less homogeneous soil microbiome, highlighting the potential of agroforestry to counteract the homogenization of the soil microbiome through agriculture.

Effect of nitrogen content and magnesium-cerium treatment on inclusions in interstitial free steel

The electric arc furnace process is beneficial for reducing carbon emission in the steelmaking industry. However, the excessive nitrogen content in electric arc furnace molten steel is unfavourable for producing high-grade interstitial free (IF) steel. In this work, the effect of nitrogen content on inclusions in IF steel and the Mg–Ce treatment modification performance were investigated through thermodynamic calculations and experimental characterisation. The results show that, as the nitrogen content in IF steel rises from 0.0025% to 0.0067%, the precipitation of TiN is promoted, leading to an increase in both the number density and the size of TiN inclusions. The average size of TiN increases from 2.61 to 4.31 μm. After Mg treatment in high-nitrogen IF steel, a significant increase in number density while a noticeable decrease in the size of TiN can be observed. After Ce treatment, the precipitation of TiN clusters embedded in large complex Ce-rich cores causes an increase in the number of large-sized inclusions, which weakens the modification effect. Moreover, after Mg–Ce combined treatment, the TiN clusters are no longer observed, inducing an obvious decrease in the average size of TiN to 2.95 μm. Results of the TiN inclusions statistics and disregistry calculations indicate that plenty of fine dispersed Mg-rich and Ce-rich inclusions can serve as the nuclei for the heterogeneous nucleation of TiN, thereby refining the inclusions.