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Study on the compaction characteristics of snow on airport runways under vertical load
Snow accumulation on airport runways reduces friction, affecting aircraft takeoff and landing performance, as well as operational efficiency and safety. Previous studies have primarily focused on the bearing capacity and mechanical properties of compacted snow. However, there is limited research on the compaction characteristics of naturally loose snow under vertical loads. This study employs the Arbitrary Lagrangian-Eulerian (ALE) method to construct a snow model based on the Modified Drucker Prager Cap (MDPC) Model, analyzing the compaction characteristics of snow under aircraft tires with varying snow thicknesses (5 mm to 50 mm) and vertical loads (250N to 2250N). The results indicate that when the snow thickness is less than the tire tread depth, the impact of vertical load on snow compaction displacement is negligible, maintaining a displacement of 3–5 mm. Conversely, when the snow thickness exceeds the tread depth, the compaction displacement increases with load until reaching a stable state. The compaction rate initially increases and then decreases with different snow thicknesses; beyond the tread depth, the load significantly affects the maximum compaction rate, which reaches 504 mm/s. Additionally, the density changes in the tire-snow contact area are influenced by both snow thickness and vertical load. As thickness and load increase, the duration for which the sidewall density exceeds that of the center also extends, with vertical load having a minimal effect on density transition.
Acute radiation exposure in mice reveals traces of oxidation-mediated modifications in serum albumin
High doses of ionizing radiation induce specific oxidation-mediated modifications on the sequence of amino acid that constitutes serum albumin, but the time-dependent response thereafter is unclear. We, therefore, used liquid chromatography coupled with tandem mass spectrometry to profile oxidation-mediated modifications in serum collected from mice subjected to total body X-ray irradiation (TBI) at 20-day intervals up to day 80. In TBI mice, albumin structural regions were generally glycated and oxidatively modified, and in particular, oxidative modifications of serum albumin (OMSA) were observed on either analysis day in eight sequences containing the following amino acid residues: OMSA9 (oxidation of lysine residue (Lys)-97), OMSA12 (oxidation of methionine residue (Met)-147), OMSA21 (oxidation of tyrosine residue (Tyr)-287), OMSA22 (oxidation of proline residue (Pro)-306), OMSA25 (oxidation of Lys-310), OMSA29 (oxidation of Pro-390), OMSA40 (oxidation of Tyr-476), and OMSA39 (nitration of Tyr-476). Interestingly, some significant OMSA sequences induced by TBI were maintained even after 41 times the half-life of albumin. These results suggest that exposure to ionizing radiation induces specific oxidative modifications in serum albumin, and there are specific amino acid residues that are sensitive to these modifications. Furthermore, these could be applied as novel biomarkers to estimate the presence or history of radiation exposure.
Harambee! 2.0: Community resources and resilience factors to leverage for improving HIV testing behaviors among African immigrant communities in Seattle, Washington
Significant challenges promoting positive HIV testing behaviors among African immigrant communities in the U.S. persist, though existing community resources may be leveraged to improving these behaviors and increasing testing uptake. We conducted 30 key informant interviews and five focus group discussions (n = total 72 participants) among members of the Ethiopian, Somali, and Eritrean communities in Seattle, WA to identify these resources. Our findings highlight the following three main themes for responsive interventions: (1) capitalize on religious leaders and institutions as key facilitators; (2) leverage existing community resources, such as ethnic community centers, health boards, and healthcare professionals; and (3) utilize existing culturally-rich media for health promotion, centering on multi-linguality, -culturality, and -generationality. Our findings suggest that a wealth of community resources and resilience factors exist to leverage to improve HIV testing behaviors among African immigrant communities in the U.S.
Thiazole-carboxamide derivatives as potent antioxidant agents with drug-like properties: In vitro, molecular docking, and DFT studies
The search for novel therapeutic agents with potent antioxidant and antidiabetic properties remains a critical area of research in medicinal chemistry. Oxidative stress, caused by an imbalance between free radicals and the body’s antioxidant defenses, is implicated in numerous diseases, including diabetes, cancer, and neurodegenerative disorders. The in vitro evaluation of the antioxidant activity and α-amylase inhibitory potential was conducted on a series of thiazole-carboxamide derivatives, among this series, the strongest antioxidant activity against the DPPH free radical was exhibited by LMH6, with an IC₅₀ value of 0.185 µM, followed by LMH7 with an IC₅₀ value of 0.221 µM. Notably, the positive control Trolox exhibited a comparatively higher IC₅₀ value of 3.10 µM, underscoring the exceptional antioxidant potential of the synthesized compounds. Upon evaluating the inhibitory potency of the LMH series against the α-amylase enzyme, as a measure of their potential antidiabetic activity, the compounds generally exhibited modest to weak activity. In this case, their inhibition profiles were notably less potent compared to the respective positive control (acarbose). Subsequently, molecular docking studies were conducted to explore potential mechanisms that may underlie the observed antioxidant and antidiabetic activities. While these in silico analyses suggest possible interactions, particularly with the Keap1 protein, they serve as complementary hypotheses rather than direct validation of the in vitro findings. Docking scores, MM-GBSA binding energies, and association patterns were recorded and studied. Also, a DFT study was conducted to gain deeper insights into the free radical scavenging potential of the most potent antioxidant in the LMH series. The evaluated thiazole-carboxamide derivative demonstrated enhanced antioxidant potential by surpassing the reference compounds in terms of EHOMO-LUMO gap, electron affinity (EA), and ionization potential (IP). It was also evaluated the druggability of the tested compounds using Lipinski’s Rule of Five (LRO5). This analysis helps determine their drug-like properties based on established physicochemical criteria. The analysis confirmed that all the derivatives (LMH1–LMH9) met the LRO5 criteria, indicating their potential as orally active drug candidates. The ideal drug-likeness characteristics of these derivatives support the findings, highlighting the need for further preclinical and biological studies. These molecules could greatly facilitate future therapeutic research and approval due to their beneficial properties.
Low survival in younger adults with Acute Myeloid Leukemia (AML) in Tanzania linked to high disease burden and socioeconomic factors
Background Acute Myeloid Leukemia (AML) accounts for 20–25% of all leukemia diagnosed worldwide. According to Globoccan 2020, leukemia ranked the 15th most prevalent cancer with an estimated 474,519 new cases and 311,594 deaths annually. However, due to scarcity of well documented cancer registries, epidemiological and survival data of patients with AML is lacking in many African countries, including Tanzania. Therefore, the primary objective of this study was to determine the clinical features, laboratory characteristics and survival outcomes of AML patients treated with different regimens in Tanzania. Methods Data from all adult patients diagnosed with AML at Muhimbili National Hospital (MNH) between January 2018 and December 2023 were analyzed in this retrospective study. STATA version 16 was used for data analysis. The survival outcome was calculated using the Kaplan-Meier method. To evaluate the statistical significance of the results, a p-value cut-off of 0.05 was used. The Cox proportional hazards model was used to identify predictors of survival and to estimate the effect of covariates on the hazard of death. Kruskal Wallis was used to compare the median values for laboratory results and pairwise comparison of median laboratory values was done using the Dunn Test. Results A total of 245 patients were diagnosed with acute leukemia during the five-year period (2018−2023), of which 169 (68%) had AML. The mean age at diagnosis was 47.2 (SD ± 18.5) years. Majority of the patients were females (60.7%), and had de novo AML. Most of the patients presented with symptoms of anemia (98.2%) and fever (79.5%). The median survival time was 81 days with a one-year overall survival probability of 15.2%. Patients that resided outside of the Dar es Salaam region had a 74% increase hazard of mortality compared to those living within the Dar es Salaam region (aHR: 1.74, 95% CI: 1.15–2.64, p = 0.008). Patients receiving any form of chemotherapy had a 39% lower hazard of mortality compared to those who were on supportive treatment alone (aHR: 0.61, 95% CI: 0.40–0.93, p = 0.022). Conclusion AML is the most common acute leukemia among adults in Tanzania, primarily affecting young females under 50 years. Resource constraints and limited treatment options result in poor outcomes, with a median survival of 81 days and one-year overall survival of 15.2%.
Ferroelectric-based Pockels photonic memory
Production of recombinant human G protein-coupled estrogen receptor (GPER) and establishment of a ligand binding assay using graphene quantum dots (GQDs)
G protein-coupled estrogen receptor (GPER) is a member of the GPCR family and a key mediator of the rapid, nongenomic actions of estrogens as membrane estrogen receptors. In this study, we established a procedure for the expression and purification of recombinant human membrane estrogen receptor (hGPER) protein via the expression system using the methylotrophic yeast Pichia pastoris. By optimizing codon usage, we successfully expressed hGPER at a level that can be purified by column chromatography. The recombinant protein was purified via three chromatography steps. Purified hGPER showed specific estrogen-binding activity (Kd = 9.9 nM and Bmax = 1.76 nM) in a radiolabeled steroid-binding assay. We subsequently established a homogeneous assay for hGPER ligands by conjugating semiconductor nanoparticles known as graphene quantum dots (GQDs) to hGPER. GQDs coupled with hGPER (GQD-hGPER) caused a decrease in fluorescence at 520 nm from E2-BSA-FITC, which was activated by 370 nm light upon the addition of free estradiol to the reaction mixture. Fluorescence was decreased by the administration of hGPER ligands but not by steroids that do not interact with hGPER. Thus, we successfully established a ligand-binding assay for hGPER that is suitable for screening potential compounds. hGPER is a promising candidate for drug discovery for nongenomic estrogen-stimulating effects. The homogeneous assay established in this study will be usable for that purpose.
Distinct solvation patterns of OH− versus H3O+ charge defects at electrified gold/water interfaces govern their properties
Abstract Understanding the solvation structures of OH − and H 3 O + at metal interfaces is crucial for developing efficient electrochemical devices. In this paper, we present a detailed investigation of the solvation structures of OH − and H 3 O + near gold electrodes under alkaline and acidic aqueous conditions, using ab initio molecular dynamics simulations at controlled surface charge density conditions. Our findings reveal that the adsorption tendencies of OH − and H 3 O + are strongly influenced by the oscillating net atomic charge of water normal to the electrified interface in concert with the distinct solvation patterns of these charge defects. While OH − preferentially adsorbs onto the gold surface within the first water layer, the positive net atomic charge restricts the closest approach of H 3 O + to beyond the first water layer. We unveil resting and active states that support charge transfer processes at the gold/water interface, which critically involve Au atoms in a unique Grotthuss-like mechanism.
Evaluation of QIAreach QuantiFERON-TB lateral-flow nanoparticle fluorescence assay for TB infection diagnosis among TB household contacts in three high-burden settings
Background Tuberculosis infection (TBI) testing, and treatment are fundamental to achieve TB elimination. TBI testing among close or household contacts (HHCs) has been limited, in part due to perceived complexity and high operational cost. We evaluated the performance of a new near-patient and field-based QIAreach QuantiFERON-TB (QIAreach) against QuantiFERON-TB-Gold-Plus (QFT-Plus) among HHCs of people with TB. Methods A cross-sectional study was conducted from July 2021 to September 2022 in Lesotho, South Africa and Tanzania. Blood samples were collected from HHCs for paired QFT-Plus and QIAreach processing, testing and interpretation. To evaluate the performance of QIAreach against QFT-Plus as a reference, we determined the: i) prevalence of TBI, ii) total concordance using Cohen’s Kappa, iii) predictors of discordant results using logistic regression, and iv) relationship between time to results and interferon-gamma (IFN-γ) response levels using linear correlation. Results Out of 964 enrolled HHCs, 464 had paired results, of whom 64.9% (302/465) were female with a cohort median age of 27 years (interquartile range (IQR): 13–45). Overall, 50.9% (236/464) tested positive on QFT-Plus, while 57.1% (265/464) were positive on QIAreach assay. Total concordance between QFT-Plus and QIAreach was 78.4% [353/450, 95% confidence interval (CI): 74.4–82.2, Cohen’s Kappa: 0.5627, p < 0.001]. Discordance between assays was 23.9% (111/464) and was associated with Lesotho site (adjusted odds ratio 2.70, 95%CI: 1.48–4.92, p = 0.001). HHCs with higher IFN-γ response (QFT-Plus) (≥0.35 IU.ml-l) had a shorter time to results on QIAreach. In addition, a strong negative correlation between QIAreach time to results and IFN-γ response (QFT-Plus) levels (R = −0.64, 95% CI: −0.87 to −0.41, p < 0.001) was observed. Conclusion QIAreach demonstrated a moderate concordance against QFT-Plus among HHCs in three high-burden countries. Further work is needed to understand and improve its usability in high TB and low resource settings.
Detection of 85 new active subglacial lakes in Antarctica from a decade of CryoSat-2 data
Abstract Subglacial lake activity influences ice sheet flow, grounding line discharge and ice shelf basal melting. Although 146 active subglacial lakes have been detected in Antarctica via ice surface elevation change associated with their activity, only 36 fill-drain cycles have been observed worldwide, and knowledge of these mechanisms is limited. Here, we use a decade of CryoSat-2 radar altimetry to detect 85 active subglacial lakes in Antarctica, documenting 37 and 34 complete draining and filling events respectively. We delineate time-varying boundaries of subglacial lake activity and investigate their variability over time. Our observations increase the number of known active subglacial lakes in Antarctica by 58%, with six of these located within 8 km of the grounding zone. We observe five subglacial lake networks, with concurrent upstream drainage and downstream filling, and 25 clusters of lakes, improving our knowledge of interconnected subglacial hydrological pathways.
Exploratory trajectory inference reveals convergent lineages for CD8 T cells in chronic LCMV infection
Trajectory inference refers to the task of reconstructing state sequences of dynamic processes from single-cell RNA sequencing (scRNAseq) data. This task frequently results in ambiguous results due to the noisiness of the data. While this issue has been alleviated by the incorporation of directional information from RNA velocity analyses, it remains difficult to resolve complex differentiation topologies, such as convergent trajectories. We introduce exploratory trajectory inference to address this challenge. This approach considers unsupervised clustering analysis of trajectory ensembles derived from simulation-based trajectory inference to deduce differentiation lineages in a data-driven fashion. We assess this approach to resolve the convergent differentiation trajectories in CD8 T-cell differentiation in chronic infections. We utilize an original scRNAseq time-series dataset of CD8 T cells collected during the time course of a chronic LCMV infection. Simulation-based trajectory inference identified a branch region early during chronic infection where cells separate into an exhausted and a memory-like lineage. Exploratory trajectory inference further allowed us to identify a convergent differentiation trajectory traversing memory-like states and ending in the exhausted population. Adoptive transfer experiments showed CD8 T cells with predicted memory-like fate differentiating into both memory-like and exhaustion states, confirming the convergent differentiation topology. We expect exploratory trajectory inference to be applicable in other scRNAseq-based studies aiming at comprehensive characterization of differentiation trajectories with bifurcating and convergent topologies.
Thalamus enables active dendritic coupling of inputs arriving at different cortical layers
Abstract Dendritic calcium action potentials (APs) enable the main output neurons of the cerebral cortex – pyramidal tract neurons (PTs) – to associate inputs that arrive at different cortical layers. How synaptic inputs evoke calcium APs during in vivo conditions is yet unclear. We combine in vivo recordings in male rats with synaptic input reconstructions, multi-scale modelling and optogenetic manipulations. We find that thalamocortical (TC) synapses, which provide sensory input to cortex, target specifically and most densely the dendritic domain that initiates calcium APs in PTs. Sensory input from thalamus is hence a reliable, but weak source for activating the dendritic calcium domain. Because it is fast and local, this activation enables active dendritic coupling of sensory input with multiple sensory-evoked and ongoing input streams that arrive during and surprisingly before the stimulus. This ‘TC coupling’ mechanism accounts for the modulation of the first sensory responses that leave the cortex with bursts of APs.
Can you learn not to respond to irrelevant motion while making fast arm movements?
If the target of a goal-directed arm movement is suddenly displaced, the movement is quickly adjusted in accordance with the target’s new position. Such quick adjustments are even observed if the target is moving, so the arm is moving towards a future target position. If irrelevant items near that future position suddenly start moving, the arm produces a futile response in the direction of the irrelevant items’ motion. We wondered whether people could learn not to respond to such irrelevant motion. To find out, we had participants intercept targets that moved across a background consisting of hundreds of small dots (irrelevant items). At a fixed time before the target reached an interception zone, the background dots started moving. The response to this irrelevant motion declined across the first few hundred trials, but it never fully disappeared. Including trials in which the target jumped established that participants learnt to reduce their response to the irrelevant motion, rather than to reduce their response to any new information. We conclude that participants can reduce the extent to which they respond to irrelevant motion, but that they cannot suppress such responses altogether.
Genetic architecture of plasma metabolome in 254,825 individuals
Abstract Circulating metabolites are crucial to biological processes underlying health and diseases, yet their genetic determinants remain incompletely understood. Here, we investigate the genetic architecture of nuclear magnetic resonance-based metabolomics, analyzing 249 metabolic measures and 64 biologically plausible ratios in 254,825 participants. We conduct a genome-wide association study (GWAS) identifying 24,438 independent variant-metabolite associations across 427 loci, with effect sizes highly concordant with 19 previous studies. Fine-mapping pinpoints 3610 putative causal associations, 785 of which are novel. Additionally, we utilize whole exome sequencing data and uncover 2948 gene-metabolite associations through aggregate testing, underscoring the importance of rare coding variants overlooked in GWAS. Integrating our findings with disease genetics reveals potential causal associations, such as between acetate levels and the risk of atrial fibrillation and flutter. Collectively, this study delineates the complex genetic architecture of the plasma metabolome, offering a valuable resource for future investigations into disease mechanisms and therapeutic strategies.
Correction: Reconstructions of individual fish trophic geographies using isotopic analysis of eye-lens amino acids
Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation
Exploring the prevalence of severe obesity in a large teaching hospital
Background Obesity remains a critical public health issue in the Netherlands, where 50.2% of the population has a body mass index (BMI) over 25 kg/m2, 15.6% exceeds 30 kg/m2, and 3.5% meets the criteria for severe obesity (BMI ≥ 35 kg/m2). This study aimed to describe the prevalence and distribution of severe obesity across medical specialties in a large Dutch teaching hospital, to assess whether certain departments carry a disproportionate burden compared to national averages. Methods A retrospective cohort study was conducted at Catharina Hospital in Eindhoven, using patient data from 2022 and 2023. Patients with a history or current treatment for Metabolic Bariatric Surgery (MBS) were excluded. The highest registered BMI during the study period was used for analysis. Data was analyzed across specialties with attention to procedural volume and hospital burden. Additionally, all surgical procedures were reviewed in patients with BMI ≥ 35 kg/m2. Results In total, in 8.0% of all hospital visits patients had a BMI ≥ 35 kg/m2, compared to 3.5% in the general population. Specialties such as pulmonology (12.8%), internal medicine (10.4%), and orthopedic surgery (9.8%) showed a notably higher prevalence. Furthermore, a total of 5,472 surgical procedures were performed on patients with severe obesity, representing 13.5% of all surgical procedures. Common procedures included percutaneous coronary intervention in cardiology, laparoscopic cholecystectomy in general surgery, coronary artery bypass graft in cardiothoracic surgery, and total knee arthroplasty in orthopedic surgery. Conclusion Approximately one in thirteen hospital patients presents with severe obesity, and undergoes over 2,700 procedures annually, reflecting the scale at which severe obesity intersects with hospital-based healthcare. These findings emphasize the need for heightened awareness of obesity-related healthcare demands and the need for further research into the impact of severe obesity on surgical outcomes and use of hospital resources.
Author Correction: Chirality encoding in resonant metasurfaces governed by lattice symmetries
Risk prediction of all-cause mortality in hospitalized patients with severe acute pancreatitis by serum urea nitrogen/albumin ratio
Background Classification of risk levels in patients with acute pancreatitis remains a difficult task. Although some biomarkers have emerged to predict the prognosis of patients with acute pancreatitis, they have not been widely used in clinical practice for several reasons. This study aimed to investigate the correlation between the serum urea nitrogen-to-albumin ratio (BAR) and the mortality risk in ICU patients with acute pancreatitis. Method This was a retrospective study. Data were collected from the Medical Information Mart for Intensive Care IV (MIMIC IV 2.0). The primary outcome was in-hospital mortality in the patients with severe acute pancreatitis. In this study, multivariate logistic proportional regression analysis and restricted cubic spline regression were used to evaluate the association between serum urea nitrogen/albumin ratio and in-hospital mortality in patients with severe acute pancreatitis. In the sensitivity analysis, the Boruta and random forest algorithms were used to determine the feature importance of the serum urea nitrogen to albumin ratio, and subgroup analysis was used to explore the robustness of the results. Result 726 patients were included in this study. The in-hospital mortality rate was 11.85%. Multivariate logistic regression analysis revealed that BAR was independently associated with an increased risk of in-hospital mortality (odds ratio [HR], 1.081 [95% confidence interval [CI], 1.062–1.101]; P < 0.001). The restricted cubic spline regression model revealed that the risk of in-hospital mortality increased linearly with increasing BAR. Sensitivity analysis indicated that the results were stable. Additionally, the machine learning results suggested that the serum urea nitrogen to albumin ratio is an important feature for the outcomes of severe acute pancreatitis. Conclusion A high serum urea nitrogen to albumin ratio was significantly associated with in-hospital mortality in patients with severe acute pancreatitis.