Search Results (76)

As a key roadside safety feature, longitudinal guardrail steel barriers are purposefully designed to contain and redirect errant vehicles to prevent roadway departure, dissipate impact energy through plastic deformation, and reduce the severity of vehicle crashes. Nevertheless, these systems should be carefully designed and assessed, as localized rupturing, especially near splice or impact locations, can lead to catastrophic failures, compromising vehicle containment, violating crash safety standards, and ultimately jeopardizing the safety of occupants and other road users. Before conducting full-scale crash testing, finite element analysis (FEA) tools are widely employed to evaluate the design efficiency, optimize system configurations, and preemptively identify potential failure modes prior to expensive physical crash testing. To accurately assess system behavior, calibrated material models and precise failure criteria must be utilized in these simulations. Despite the existence of numerous failure criteria and material models, the material characteristics of AASHTO M-180 guardrail steel have not been fully investigated. This paper significantly advances the FE modeling of ductile fracture in guardrail steel, addressing a critical need within the roadside safety community. This study formulates stress-state-dependent failure criteria and proposes advanced material modeling techniques. Extensive experimental testing was conducted on steel specimens having various triaxiality and Lode parameter values to reproduce a wide spectrum of complex, three-dimensional stress-state loading conditions. The test results were then used to identify material properties and construct a failure surface. Subsequent FEA, which incorporated the Generalized Incremental Stress-State-Dependent Damage Model (GISSMO) in conjunction with two LS-DYNA material models, illustrates the capability of the developed surface and material input parameters to predict material behavior under various stress states accurately. A parametric study was completed to further validate the proposed models, highlighting their robustness and reliability. Full article

Brake wear emissions can be reduced by altering the surface of brake disks. A parametric study using a gray cast iron and a laser-cladded brake disk was performed in a pin-on-disk experiment with integrated optical pin surface characterization and particle emission measurement. Significant differences in the friction, wear and emission behavior are present. The high wear-resistance of the laser-cladded disk led to a reduction of 70% of the particle number emission relative to the gray cast iron disk, but the coefficient of friction was unstable. The surface of the pin used with the gray cast iron showed an initial large debris extension and protruding patches that were removed at high braking energies, exposing white patches and creating holes. These observations correspond to known processes from the plateau theory. The surface of the pin used with the laser-cladded disk showed a topography dominated by holes with almost no protruding patches. The braking condition did not influence the pin surface, implying that the disk and not solely the pin surface might be governing the friction process, and therefore challenging the applicability of the plateau theory to laser-cladded disks. To further study this aspect, a segmentation method was developed for the pin surface images and topographical data to extract and quantify different features on the pin, such as debris, patches, holes and the tribolayer. The correlation of the surface coverage ratios of the feature classes with the braking conditions (speed and applied pressure), the coefficient of friction and the emissions confirmed the differences between the gray cast iron and laser-cladded brake disk. Full article

Anaerobic digesters fed with dairy cow slurry struggle to achieve economic viability, particularly when animals are housed seasonally, so additional feedstocks are usually required. This study applied experimentally derived data from the co-digestion of cow slurry (CS) and food waste (FW) to the UK dairy herd as a whole, and at average (AH) and large (LH) herd sizes of 160 and 770 animals, respectively. The experimental data confirmed stable operation at an organic loading rate (OLR) of 5 g VS L⁻¹ day⁻¹ at CS:FW ratios of 3:1 and 6:1 on a wet weight basis, and these parameters were considered for both AH and LH by herd size and country (Scotland, England, Wales, Northern Ireland) in order to provide energy production and policy observations. The results showed that these scenarios could provide between 959 to 23,867 GJ per year, and that a targeted policy intervention could affect slurry treatment from a significant number of animals in a relatively small number of large herds across the UK. For a more detailed analysis, better data are required on non-domestic FW arisings and FW transportation needs. Full article

Purpose: To investigate the effect of vitamin C supplementation with or without flavonoids on periodontal conditions, and microbial and systemic variables before and after non-surgical periodontal treatment (NSPT). Materials and Methods: A case series derived from a randomized controlled trial was conducted to explore the effects of daily vitamin C supplementation, with or without flavonoids, on periodontal conditions. The study population was recruited from patients with periodontitis who had been referred to the Department of Periodontology at the Academic Centre for Dentistry Amsterdam (ACTA). The study consisted of a 2-month observation of untreated periodontitis followed by a 3-month period after NSPT. Descriptive statistics, correlation and clustering analyses, and dimensionality reduction methods were used to evaluate the interventions’ impact. Results: Due to COVID-19, the study was prematurely terminated and reported findings from 13 patients. Results indicate a correlation between higher plasma vitamin C levels and reduced gingival inflammation, suggesting benefits for untreated periodontal conditions. Clustering analysis showed no differences based on supplementation type, indicating it did not affect outcomes, and microbiological data had limited effects. Principal Component Analysis visualized clusters and illustrated no distinct groups corresponding to supplementation types. Violin plots highlighted variability, with one cluster comprising individuals with more severe periodontal conditions. Conclusions: Higher plasma vitamin C levels were associated with lower gingival inflammation. However, daily vitamin C supplementation, with or without flavonoids, did not show additional benefits on periodontal conditions before or after treatment. Clustering suggests that periodontal severity, rather than supplementation, influenced patient profiles. The study’s small sample size limits the generalizability of the findings. Full article

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732–0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502–0.698) and PFT (aOR 0.816, 95% CI 0.694–0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103–1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750–0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911–1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930–1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC. Full article

Although corn is the most important and nitrogen (N)-fertilized crop, there is a lack of long-term data on the effects of organic and inorganic N fertilizers on the N balance and losses for corn systems under different tillage approaches. From 2012 to 2023, we assessed the effects of the N source on the grain yields from cultivated continuous corn receiving irrigation at a site with minimal erosion in Fort Collins, Colorado, USA, and compared these effects to no-till (NT) and strip till (ST) systems receiving inorganic N. An N balance accounting for N and carbon (C) sequestration found a system nitrogen use efficiency (NUE_Sys) for organic N fertilizer (manure) with a tillage of 86.6%, which was higher than the NUE_Sys of 62.6% with inorganic N fertilizer (enhanced efficiency fertilizer, EEF). Conventional tillage with manure use is a good management practice that contributed to higher grain yields (2 of 11 years), C sequestration (p < 0.05), soil organic N content (p < 0.05), and soil phosphorus (P) content than inorganic N fertilizer with tillage (p < 0.05). The tilled systems, whether receiving organic or inorganic N fertilizer, had higher yields and grain N content than the NT and ST systems receiving inorganic N fertilizer (p < 0.05). The grain production of the cultivated system receiving organic N fertilizer did not decrease with time, while the yields of the cultivated system receiving inorganic N fertilizer decreased with time (p < 0.05), suggesting that cultivated systems receiving organic N fertilizer may be more sustainable and better able to adapt to a changing climate. Additionally, a combination of manure (30% of N input) with EEF (70% of N input) contributed to a synergistic effect that increased the agronomic productivity (harvested grain yields). Full article

DNA-binding protein A (DbpA) belongs to the Y-box family of cold shock domain (CSD) proteins that bind RNA/DNA and exert intracellular functions in cell stress, proliferation, and differentiation. Given the pattern of DbpA staining in inflammatory glomerular diseases, without adherence to cell boundaries, we hypothesized extracellular protein occurrence and specific functions. Lipopolysaccharide and ionomycin induce DbpA expression and secretion from melanoma and mesangial cells. Unlike its homologue Y-box-binding protein 1 (YB-1), DbpA secretion requires inflammasome activation, as secretion is blocked upon the addition of a NOD-like receptor protein-3 (NLRP3) inhibitor. The addition of recombinant DbpA enhances melanoma cell proliferation, migration, and competes with tumor necrosis factor (TNF) binding to its receptor (TNFR1). In TNF-induced cell death assays, rDbpA initially blocks TNF-induced apoptosis, whereas at later time points (>24 h), cells are more prone to die. Given that CSD proteins YB-1 and DbpA fulfill the criteria of alarmins, we propose that their release signals an inherent danger to the host. Some data hint at an extracellular complex formation at a ratio of 10:1 (DbpA:YB-1) of both proteins. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Peptide receptor radionuclide therapy (PRRT) using ¹⁷⁷Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of ¹⁷⁷Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT. Full article

The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial–mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein. Full article

Extracellular vesicles (EVs) are tools for intercellular communication, mediating molecular transport processes. Emerging studies have revealed that EVs are significantly involved in immune processes, including sepsis. Sepsis, a dysregulated immune response to infection, triggers systemic inflammation and multi-organ dysfunction, posing a life-threatening condition. Although extensive research has been conducted on animals, the complex inflammatory mechanisms that cause sepsis-induced organ failure in humans are still not fully understood. Recent studies have focused on secreted exosomes, which are small extracellular vesicles from various body cells, and have shed light on their involvement in the pathophysiology of sepsis. During sepsis, exosomes undergo changes in content, concentration, and function, which significantly affect the metabolism of endothelia, cardiovascular functions, and coagulation. Investigating the role of exosome content in the pathogenesis of sepsis shows promise for understanding the molecular basis of human sepsis. This review explores the contributions of activated immune cells and diverse body cells’ secreted exosomes to vital organ dysfunction in sepsis, providing insights into potential molecular biomarkers for predicting organ failure in septic shock. Full article

The Central Valley of California is one of the most prolific agricultural regions in the world. Agriculture is reliant on the conjunctive use of surface-water and groundwater. The lack of available surface-water and land-use changes have led to pumping-induced groundwater-level and storage declines, land subsidence, changes to streamflow and the environment, and the degradation of water quality. As a result, in part, the Sustainable Groundwater Management Act (SGMA) was developed. An examination of the components of SGMA and contextualizing regional model applications within the SGMA framework was undertaken to better understand and quantify many of the components of SGMA. Specifically, the U.S. Geological Survey (USGS) updated the Central Valley Hydrologic Model (CVHM) to assess hydrologic system responses to climatic variation, surface-water availability, land-use changes, and groundwater pumping. MODFLOW-OWHM has been enhanced to simulate the timing of land subsidence and attribute its inelastic and elastic portions. In addition to extending CVHM through 2019, the new version, CVHM2, includes several enhancements as follows: managed aquifer recharge (MAR), pumping with multi-aquifer wells, inflows from ungauged watersheds, and more detailed water-balance subregions, streamflow network, diversions, tile drains, land use, aquifer properties, and groundwater level and land subsidence observations. Combined with historical approximations, CVHM2 estimates approximately 158 km³ of storage loss in the Central Valley from pre-development to 2019. About 15% of the total storage loss is permanent loss of storage from subsidence that has caused damage to infrastructure. Climate extremes will likely complicate the efforts of water managers to store more water in the ground. CVHM2 can provide data in the form of aggregated input datasets, simulate climatic variations and changes, land-use changes or water management scenarios, and resulting changes in groundwater levels, storage, and land subsidence to assist decision-makers in the conjunctive management of water supplies. Full article

Microdroplet resonators provide an excellent tool for optical studies of water, but water microdroplets are difficult to maintain outside a carefully controlled environment. We present a method for maintaining a water microdroplet resonator on a 3D-printed hydrophobic surface in an ambient environment. The droplet is maintained through a passive microfluidic system that supplies water to the droplet through a vertical channel at a rate equivalent to its evaporation. In this manner, we are able to create and passively maintain water microdroplet resonators with quality factors as high as $3\times {10}^8$. Full article

The use of metabolically stabilized, radiolabeled somatostatin (SST) analogs ([⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-TATE/TOC/NOC) is well established in nuclear medicine. Despite the pivotal role of these radioligands in the diagnosis and therapy of neuroendocrine tumors (NETs), their inability to interact with all five somatostatin receptors (SST_1–5R) limits their clinical potential. [¹¹¹In]In-AT2S is a radiolabeled DOTA-conjugate derived from the parent peptide SST-14 that exhibits high binding affinity to all SSTR subtypes, but its poor metabolic stability represents a serious disadvantage for clinical use. In order to address this issue, we have replaced strategic trans-amide bonds of [¹¹¹In]In-AT2S with metabolically stable 1,4-disubstituted 1,2,3-triazole bioisosteres. From the five cyclic triazolo-peptidomimetics investigated, only [¹¹¹In]In-XG1 combined a preserved nanomolar affinity for the SST_1,2,3,5R subtypes in vitro and an improved stability in vivo (up to 17% of intact peptide 5 min postinjection (pi) versus 6% for [¹¹¹In]In-AT2S). The involvement of neprilysin (NEP) in the metabolism of [¹¹¹In]In-XG1 was confirmed by coadministration of Entresto^®, a registered antihypertensive drug, in vivo releasing the selective and potent NEP-inhibitor sacubitrilat. A pilot SPECT/CT imaging study conducted in mice bearing hSST₂R-positive xenografts failed to visualize the xenografts due to the pronounced kidney uptake (>200% injected activity (IA)/g at 4 h pi), likely the result of the formation of cationic metabolites. To corroborate the imaging data, the tumors and the kidneys were excised and analyzed with a γ-counter. Even if receptor-specific tumor uptake for [¹¹¹In]In-XG1 could be confirmed (1.61% IA/g), further optimization is required to improve its pharmacokinetic properties for radiotracer development. Full article

Background: Fibrosis is characterized by excessive extracellular matrix formation in solid organs, disrupting tissue architecture and function. The Y-box binding protein-1 (YB-1) regulates fibrosis-related genes (e.g., Col1a1, Mmp2, and Tgfβ1) and contributes significantly to disease progression. This study aims to identify fibrogenic signatures and the underlying signaling pathways modulated by YB-1. Methods: Transcriptomic changes associated with matrix gene patterns in human chronic kidney diseases and murine acute injury models were analyzed with a focus on known YB-1 targets. Ybx1-knockout mouse strains (Ybx1^ΔRosaERT+TX and Ybx1^ΔLysM) were subjected to various kidney injury models. Fibrosis patterns were characterized by histopathological staining, transcriptome analysis, qRT-PCR, methylation analysis, zymography, and Western blotting. Results: Integrative transcriptomic analyses revealed that YB-1 is involved in several fibrogenic signatures related to the matrisome, the WNT, YAP/TAZ, and TGFß pathways, and regulates Klotho expression. Changes in the methylation status of the Klotho promoter by specific methyltransferases (DNMT) are linked to YB-1 expression, extending to other fibrogenic genes. Notably, kidney-resident cells play a significant role in YB-1-modulated fibrogenic signaling, whereas infiltrating myeloid immune cells have a minimal impact. Conclusions: YB-1 emerges as a master regulator of fibrogenesis, guiding DNMT1 to fibrosis-related genes. This highlights YB-1 as a potential target for epigenetic therapies interfering in this process. Full article