Miracle-dz/UniFAR-FTUs huggingface dataset:
Disturbing the Spatial Organization of Biofilm Communities Affects Expression of agr-Regulated Virulence Factors in Staphylococcus aureus

Bacteria, such as Staphylococcus aureus, integrate signals from the environment to regulate genes encoding virulence factors. These signals include those produced by quorum-sensing systems and nutrient availability. ABSTRACT Staphylococcus aureus uses quorum sensing and nutrient availability to control the expression of agr-regulated virulence factors. Quorum sensing is mediated by autoinducing peptide (AIP), which at a high concentration reduces expression of surface attachment proteins (coa, fnbpA) and increases expression of exotoxins (lukS) and proteases (splA). Nutrient availability can be sensed through the saeS/saeR system. Low nutrients increase expression of saeR, which augments expression of coa and fnbpA, distinct from the activity of AIP. The formation of spatial structure, such as biofilms, can alter quorum sensing and nutrient acquisition. In natural environments, biofilms encounter forces that may alter their spatial structure. These forces may impact quorum sensing and/or nutrient acquisition and thus affect the expression of agr-regulated virulence factors. However, this has not been studied. We show that periodically disturbing biofilms composed of S. aureus using a physical force affected the expression of agr-regulated virulence factors. In nutrient-poor environments, disturbance increased the expression of coa, fnbpA, lukS, and splA. Disturbance in a nutrient-rich environment at low or high disturbance amplitudes moderately reduced expression of coa and fnbpA but increased expression of lukS and splA. Interestingly, at an intermediate amplitude, the overall expression of agr-regulated virulence factors was the lowest; expression of lukS and splA remained unchanged relative to an undisturbed biofilm, while expression of coa and fnbpA significantly decreased. We hypothesize that these changes are a result of disturbance-driven changes in access to AIP and nutrients. Our results may allow the identification of environments where virulence is enhanced, or reduced, owing to a disturbance. IMPORTANCE Bacteria, such as Staphylococcus aureus, integrate signals from the environment to regulate genes encoding virulence factors. These signals include those produced by quorum-sensing systems and nutrient availability. We show that disturbing the spatial organization of S. aureus populations can lead to changes in the expression of virulence factors, likely by altering the ways in which S. aureus detects these signals. Our work may allow us to identify environments that increase or reduce the expression of virulence factors in S. aureus.
Shuffling the yeast genome using CRISPR/Cas9-generated DSBs that target the transposable Ty1 elements

Although homologous recombination between transposable elements can drive genomic evolution in yeast by facilitating chromosomal rearrangements, the details of the underlying mechanisms are not fully clarified. In the genome of the yeast Saccharomyces cerevisiae, the most common class of transposon is the retrotransposon Ty1. Here, we explored how Cas9-induced double-strand breaks (DSBs) directed to Ty1 elements produce genomic alterations in this yeast species. Following Cas9 induction, we observed a significant elevation of chromosome rearrangements such as deletions, duplications and translocations. In addition, we found elevated rates of mitotic recombination, resulting in loss of heterozygosity. Using Southern analysis coupled with short- and long-read DNA sequencing, we revealed important features of recombination induced in retrotransposons. Almost all of the chromosomal rearrangements reflect the repair of DSBs at Ty1 elements by non-allelic homologous recombination; clustered Ty elements were hotspots for chromosome rearrangements. In contrast, a large proportion (about three-fourths) of the allelic mitotic recombination events have breakpoints in unique sequences. Our analysis suggests that some of the latter events reflect extensive processing of the broken ends produced in the Ty element that extend into unique sequences resulting in break-induced replication. Finally, we found that haploid and diploid strain have different preferences for the pathways used to repair double-stranded DNA breaks. Our findings demonstrate the importance of DNA lesions in retrotransposons in driving genome evolution.
Reliable wet-chemical cleaning of natively oxidized high-efficiency Cu(In,Ga)Se2 thin-film solar cell absorbers

Currently, Cu-containing chalcopyrite-based solar cells provide the highest conversion efficiencies among all thin-film photovoltaic (PV) technologies. They have reached efficiency values above 20%, the same performance level as multi-crystalline silicon-wafer technology that dominates the commercial PV market. Chalcopyrite thin-film heterostructures consist of a layer stack with a variety of interfaces between different materials. It is the chalcopyrite/buffer region (forming the p-n junction), which is of crucial importance and therefore frequently investigated using surface and interface science tools, such as photoelectron spectroscopy and scanning probe microscopy. To ensure comparability and validity of the results, a general preparation guide for “realistic” surfaces of polycrystalline chalcopyrite thin films is highly desirable. We present results on wet-chemical cleaning procedures of polycrystalline Cu(In1-xGax)Se2 thin films with an average x = [Ga]/([In] + [Ga]) = 0.29, which were exposed to a.
Effect of charged polyelectrolytes on the electrophoretic behavior, stability, and viscoelastic properties of montmorillonite suspensions

This work is devoted to the study of the rheological properties of sodium montmorillonite suspensions in aqueous media containing polyelectrolytes in solution. Two different polyelectrolytes are employed: polyacrylic acid (PAA) and polyethyleneimine (PEI). PAA can bear negative charge, thus acting as a polyanion, while PEI can be considered as a polycation, although the charge of both polymers is strongly dependent on pH of the solution. The rheological behavior of clay suspensions is essentially determined by the electric potential of the faces and edges of the laminar clay particles. In order to analyze the changes in the interfacial electric potential of clay surfaces, the zeta potential of clay particles was estimated from electrophoresis measurements for different solution compositions. The yield stress and the storage modulus of the suspensions were determined demonstrating that only in some cases the storage modulus can be correlated with the changes in electrostatic interactions between particles.
Low-cost prosthetic feet for underserved populations: A comparison of gait analysis and mechanical stiffness

Background: Lower-limb loss is an ongoing cause of disability throughout the world. Despite advancements in prosthetic technologies, there are numerous underserved populations in need of effective low-cost prosthetic foot options. Objective: To evaluate the biomechanical performance of several low-cost prosthetic feet, using a combination of instrumented gait analysis and mechanical stiffness testing. Study design: Randomized crossover with additional case study. Methods: We compared the solid-ankle-cushioned-heel (SACH), Jaipur, and Niagara feet with carbon fiber feet. Mechanical stiffness was evaluated using a cantilever-style bending test at 2 angles that was designed to mimic late stance gait loading. Eight below-knee amputees participated in the gait analysis, which focused on foot and ankle motion and energetics. Results: Metric analysis showed significant differences among feet in ankle motion and power as well as distal-to-shank power, with SACH showing reduced ankle motion and positive work compared with the other feet. Waveform analysis additionally revealed a compensatory knee flexion moment in SACH and a knee extension moment in Niagara and Jaipur during midstance. In mechanical stiffness testing, SACH had the highest stiffness, with Niagara and carbon fiber roughly similar, and Jaipur the most compliant with the greatest hysteresis. Conclusions: There may be an optimal stiffness range for future prosthesis designs that maximizes propulsive energy. This may be achieved by combining some characteristics of Jaipur and Niagara feet in new designs. Ultimately, optimizing stiffness and energetics for gait biomimicry while maintaining cost, availability, and versatility across cultures will alleviate the effects of limb loss among underserved populations.
Noninvasive serum biomarkers for liver steatosis in nonalcoholic fatty liver disease: Current and future developments

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of the population worldwide and includes nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis. Since NAFLD-associated diseases begin with steatosis, the early diagnosis of steatosis helps to prevent the progression of NASH and fibrosis. In addition, more convenient and easily diagnosable serum biomarkers are becoming crucial in disease diagnosis. In this report, we summarize the known serum biomarkers for liver steatosis and provide guidance for their application in clinical practice.
Ionic Conduction in Polymer‐Based Solid Electrolytes

Good safety, high interfacial compatibility, low cost, and facile processability make polymer‐based solid electrolytes promising materials for next‐generation batteries. Key issues related to polymer‐based solid electrolytes, such as synthesis methods, ionic conductivity, and battery architecture, are investigated in past decades. However, mechanistic understanding of the ionic conduction is still lacking, which impedes the design and optimization of polymer‐based solid electrolytes. In this review, the ionic conduction mechanisms and optimization strategies of polymer‐based solid electrolytes, including solvent‐free polymer electrolytes, composite polymer electrolytes, and quasi‐solid/gel polymer electrolytes, are summarized and evaluated. Challenges and strategies for enhancing the ionic conductivity are elaborated, while the ion‐pair dissociation, ion mobility, polymer relaxation, and interactions at polymer/filler interfaces are highlighted. This comprehensive review is especially pertinent for the targeted enhancement of the Li‐ion conductivity of polymer‐based solid electrolytes.
Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66–83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor–ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-γ stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.
A virtual boundary method with improved computational efficiency using a multi‐grid method

The flow around spherical, solid objects is considered. The boundary conditions on the solid boundaries have been applied by replacing the boundary with a surface force distribution on the surface, such that the required boundary conditions are satisfied. The velocity on the boundary is determined by extrapolation from the flow field. The source terms are determined iteratively, as part of the solution. They are then averaged and are smoothed out to nearby computational grid points. A multi‐grid scheme has been used to enhance the computational efficiency of the solution of the force equations. The method has been evaluated for flow around both moving and stationary spherical objects at very low and intermediate Reynolds numbers. The results shows a second order accuracy of the method both at creeping flow and at Re=100. The multi‐grid scheme is shown to enhance the convergence rate up to a factor 10 as compared to single grid approach. Copyright © 2004 John Wiley & Sons, Ltd.
Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism

Objective: Idiopathic hypogonadotropic hypogonadism (IHH) is classified into two groups-Kalman syndrome and normosmic IHH (nIHH). Half of all cases can be explained by mutations in >50 genes. Targeted gene panel testing with nexrt generation sequencing (NGS) is required for patients without typical phenotypic findings. The aim was to determine the genetic etiologies of patients with IHH using NGS, including 54 IHH-associated genes, and to present protein homology modeling and protein stability analyzes of the detected variations. Methods: Clinical and demographic data of 16 patients (eight female), aged between 11.6-17.8 years, from different families were assessed. All patients were followed up for a diagnosis of nIHH, had normal cranial imaging, were without anterior pituitary hormone deficiency other than gonadotropins, had no sex chromosome anomaly, had no additional disease, and underwent genetic analysis with NGS between the years 2008-2021. Rare variants were classified according to the variant interpretation framework of the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology. Changes in protein structure caused by variations were modeled using RoseTTAFold and changes in protein stability resulting from variation were analyzed. Results: Half of the 16 had no detectable variation. Three (18.75%) had a homozygous (pathogenic) variant in the GNRHR gene, one (6.25%) had a compound heterozygous [likely pathogenic-variants of uncertain significance (VUS)] variant in PROK2 and four (25%) each had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH. Conclusion: The frequency of variation detection was similar to the literature. Modelling showed that the variant in five different genes, interpreted as VUS according to ACMG, could explain the clinical IHH.
Validity of constructed-response situational judgment tests in training programs for the health professions: A systematic review and meta-analysis protocol

Background Situational judgments tests have been increasingly used to help training programs for the health professions incorporate professionalism attributes into their admissions process. While such tests have strong psychometric properties for testing professional attributes and are feasible to implement in high-volume, high-stakes selection, little is known about constructed-response situational judgment tests and their validity. Methods We will conduct a systematic review of primary published or unpublished studies reporting on the association between scores on constructed-response situational judgment tests and scores on other tests that measure personal, interpersonal, or professional attributes in training programs for the health professions. In addition to searching electronic databases, we will contact academics and researchers and undertake backward and forward searching. Two reviewers will independently screen the papers and decide on their inclusion, first based on the titles and abstracts of all citations, and then according to the full texts. Data extraction will be done independently by two reviewers using a data extraction form to chart study details and key findings. Studies will be assessed for the risk of bias and quality by two reviewers using the “Quality In Prognosis Studies” tool. To synthesize evidence, we will test the statistical heterogeneity and conduct a psychometric meta-analysis using a random-effects model. If adequate data are available, we will explore whether the meta-analytic correlation varies across different subgroups (e.g., race, gender). Discussion The findings of this study will inform best practices for admission and selection of applicants for training programs for the health professions and encourage further research on constructed-response situational judgment tests, in particular their validity. Trial registration The protocol for this systematic review has been registered in PROSPERO [CRD42022314561]. https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42022314561.
COVID-19 vaccination hesitancy among Italian parents: A systematic review and meta-analysis

ABSTRACT In May 2021, the Italian government extended the COVID-19 vaccination campaign to 12- to 18-year-old subjects and, starting December 2021, vaccines were also offered to children between 5 and 11 years-old. Despite these efforts, suboptimal vaccination coverages are reported. The purpose of this review is to estimate the proportion of parents/caregivers of children and adolescents expressing COVID-19 vaccine hesitancy in Italy. The vaccine hesitation rate among parents of minors was 55.1% (95%CI: 43.8–66.1%). A higher value was evidenced in studies focusing on children (59.9%; 95%CI = 43.7–75.1%) compared to the ones focusing on adolescents (51.3%; 95%CI = 34.5–68.0%). The main reasons for unwillingness were the belief that the vaccine was unsafe or ineffective, fear of adverse events, and considering COVID-19 a non-threatening disease. The implementation of effective communication campaigns and health educational programs on safe pediatric vaccinations is essential to support strategies to bolster vaccination confidence.
Application of the Jacobian-Free Newton-Krylov Method to Nonlinear Acceleration of Transport Source Iteration in Slab Geometry

Abstract The use of the Jacobian-free Newton-Krylov (JFNK) method within the context of nonlinear diffusion acceleration (NDA) of source iteration is explored. The JFNK method is a synergistic combination of Newton’s method as the nonlinear solver and Krylov methods as the linear solver. JFNK methods do not form or store the Jacobian matrix, and Newton’s method is executed via probing the nonlinear discrete function to approximate the required matrix-vector products. Current application of NDA relies upon a fixed-point, or Picard, iteration to resolve the nonlinearity. We show that the JFNK method can be used to replace this Picard iteration with a Newton iteration. The Picard linearization is retained as a preconditioner. We show that the resulting JFNK-NDA capability provides benefit in some regimes. Furthermore, we study the effects of a two-grid approach, and the required intergrid transfers when the higher-order transport method is solved on a fine mesh compared to the low-order acceleration problem.
Modeling the Earth's magnetospheric magnetic field confined within a realistic magnetopause

Empirical data-based models of the magnetospheric magnetic field have been widely used during recent years. However, the existing models (Tsyganenko, 1987, 1989a) have three serious deficiencies: (1) an unstable “de facto” magnetopause, (2) a crude parametrization by the Kp index, and (3) inaccuracies in the equatorial magnetotail Bz values. This paper describes a new approach to the problem; the essential new features are (1) a realistic shape and size of the magnetopause, based on fits to a large number of observed crossings (allowing a parametrization by the solar wind pressure), (2) fully controlled shielding of the magnetic field produced by all magnetospheric current systems, (3) new flexible representations for the tail and ring currents, and (4) a new “directional” criterion for fitting the model field to spacecraft data, providing improved accuracy for field line mapping. Results are presented from initial efforts to create models assembled from these modules and calibrated against spacecraft data sets.
Gut Microbial Succession Patterns and Metabolic Profiling during Pregnancy and Lactation in a Goat Model

Our findings revealed that the activity of Family_XIII_AD3011_group and Corynebacterium is strongly correlated with the beneficial regulation of physiological hormones and metabolic changes during pregnancy and lactation. These findings are key for guiding targeted microbial therapeutic approaches to modulate microbiomes in gestating and lactating mammals. ABSTRACT The maternal gut microbiome affects the duration of pregnancy, delivery, and lactation. It also coordinates the stability of maternal metabolism by regulating and modulating inflammatory cytokines and reproductive hormones. This has been shown in several species; however, the situation in ruminants remains a black box. Here, we aimed to elucidate the relationship between the hindgut microbiota, metabolism, and reproductive hormones in domestic goats (Capra hircus) during nonpregnancy, pregnancy, and lactation stages. The hindgut microbiota was altered during these three stages, with a drastic decrease in the abundance of Family_XIII_AD3011_group in the second and third trimesters of pregnancy. Additionally, a decline in the abundance of Christensenellaceae_R-7_group and Turicibacter was observed from the nonpregnancy stage to late gestation. Family_XIII_AD3011_group and Paeniclostridium were strongly correlated with decreased fecal estradiol and progesterone. Furthermore, we generated a metabolome atlas of the gut and serum from nonpregnancy to lactation to reveal the specific metabolic fingerprints of each physiological stage. Several specific gut metabolites, including carnitine C8:1, γ-aminobutyric acid, and indole-3-carboxylic acid, were negatively correlated with the fecal and serum estradiol concentrations. In contrast, 2′-deoxyinosine, deoxyadenosine, and 5′-deoxyadenosine were positively correlated with the fecal and serum estradiol concentrations. The levels of 2′-deoxyinosine, deoxyadenosine, and 5′-deoxyadenosine in fecal samples were positively correlated with Family_XIII_AD3011_group. Other serum metabolites, such as (±)12-HEPE (hydroxy eicosapentaenoic acid), (±)15-HEPE, (±)18-HEPE, cytidine, uracil, and 5-hydroxyindole-3-acetic acid, were negatively correlated with the serum concentrations of estradiol and progesterone. Finally, Corynebacterium and Clostridium_sensu_stricto_1 in the fecal samples were positively correlated with the abundance of 11,12-EET (epoxy-eicosatrienoic acid), (±)18-HEPE, (±)15-HEPE, and (±)12-HEPE in the serum. IMPORTANCE Our findings revealed that the activity of Family_XIII_AD3011_group and Corynebacterium is strongly correlated with the beneficial regulation of physiological hormones and metabolic changes during pregnancy and lactation. These findings are key for guiding targeted microbial therapeutic approaches to modulate microbiomes in gestating and lactating mammals.
Recursive self-tuning algorithm for adaptive Kalman filtering

A new recursive algorithm for adaptive Kalman filtering is proposed. The signal state-space model and its noise statistics are assumed to depend on an unknown parameter taking values in a subset [', '] of Rs. The parameter is estimated recursively using the gradient of the innovation sequence of the Kalman filter. The unknown parameter is replaced by its current estimate in the Kalman-filtering algorithm. The asymptotic properties of the adaptive Kalman filter are discussed.