Miracle-dz/UniFAR-FTUs huggingface dataset:
AP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity

Follicular T helper (Tfh) cells coordinate optimal germinal center responses, but abnormal Tfh cell function contributes to autoantibody-dependent autoimmunity. Seth et al. demonstrate that AP-1–independent NFAT gene expression, typically associated with hyporesponsive T cells, is required for Tfh cell maintenance and is a therapeutic target in murine lupus.
Characterization of the coupling mechanism of scorpion β-neurotoxins on the voltage-gated sodium channel hNav1.6

Abstract Scorpion β-neurotoxins represent a pharmacological group that affects voltage-gated sodium channels (Nav). Despite knowing the electrophysiological effect of these toxins on Nav channels, the molecular mechanism by which the union is carried out is still undetermined. In this study, computational techniques such as modeling, docking and molecular dynamics were used to elucidate the mechanism of interaction between scorpion β-neurotoxins using the neurotoxin nCssII and its recombinant variant CssII-RCR, which bind to the site-4, an extracellular receptor, of the human sodium channel hNav1.6. Different modes of interaction were observed for both toxins, where the main distinguishing feature was the interaction generated by the residue E15 on such site-4; that is, E15 in nCssII exhibits an interaction with the voltage-sensing domain II, and the same residue E15 of CssII-RCR exhibits an interaction with domain III. Despite this difference in interaction by E15, it is seen that both neurotoxins interact with similar regions of the voltage sensing domain such as the S3-S4 connecting loop (L834-E838) of the hNav1.6. Our simulations present a first approach to the mode of interaction of scorpion beta-neurotoxins in toxin-receptor complexes, being able to explain at the molecular level the phenomenon of voltage sensor entrapment generated by these toxins. Communicated by Ramaswamy H. Sarma
Measures of location and scale for velocities in clusters of galaxies. A robust approach

The novel estimators proposed for the kinematical properties of clusters of galaxies are both resistant in the presence of outliers and robust for a broad range of non-Gaussian underlying populations. Extensive simulations for a number of common situations realizable in small-to-large samples of cluster radial velocities allow the identification of minimum variance estimators. Also explored is the estimation of confidence intervals, using the jacknife and bootstrap resampling techniques. These methods are compared to simple formulas based on sample estimates of central location and scale. Estimators of confidence intervals on scale require resampling. 61 refs.
Modeling the Beam Deflection of a Gantry Crane under Load

AbstractGantry cranes load and unload containers from container ships. To ensure safety and operation, the deflection of their main beams under load should be analyzed. This deflection depends on the weight of the loaded container as well as on the position of the trolley that moves the container. For this study, a bivariate polynomial model is built to estimate the deflection based on these two inputs. This two-dimensional load-dependent model is developed in four steps in order to determine the shape of the deflection (dependent on the trolley position) as well as its magnitude (dependent on the container weight). A specific gantry crane was monitored with several sensors where five are inclinometer sensors that observe the tilt along the crane’s main beam and two are tacheometers that observe the trolley position and the absolute deflection. By collecting data from 18 loading operations, the parameters of the deflection model are estimated. Based on this data, the deflection under load is processed dep.
Extensive crop–wild hybridization during Brassica evolution and selection during the domestication and diversification of Brassica crops

Abstract Adaptive genetic diversity in crop wild relatives (CWRs) can be exploited to develop improved crops with higher yield and resilience if phylogenetic relationships between crops and their CWRs are resolved. This further allows accurate quantification of genome-wide introgression and determination of regions of the genome under selection. Using broad sampling of CWRs and whole genome sequencing, we further demonstrate the relationships among two economically valuable and morphologically diverse Brassica crop species, their CWRs, and their putative wild progenitors. Complex genetic relationships and extensive genomic introgression between CWRs and Brassica crops were revealed. Some wild Brassica oleracea populations have admixed feral origins; some domesticated taxa in both crop species are of hybrid origin, while wild Brassica rapa is genetically indistinct from turnips. The extensive genomic introgression that we reveal could result in false identification of selection signatures during domestication using traditional comparative approaches used previously; therefore, we adopted a single-population approach to study selection during domestication. We used this to explore examples of parallel phenotypic selection in the two crop groups and highlight promising candidate genes for future investigation. Our analysis defines the complex genetic relationships between Brassica crops and their diverse CWRs, revealing extensive cross-species gene flow with implications for both crop domestication and evolutionary diversification more generally.
Scatter Correction Method for Cone Beam CT Using Beam Attenuation Grid

The scattering phenomenon has an important influence on the reconstructed image in Cone Beam CT (CBCT) imaging systems, and is a long-lasting research topic on CBCT. Focusing on the scatter artifact in the cone beam CT system, we proposed a new scatter correction method that needed to add a beam attenuation grid (BAG) between the X - ray source and the tested object. This study educed the scatter correction algorithm based on the Beer theorem. Through subtracting the scatter distribution image from the original projection image, we can acquire the scatter-corrected projection Images of the tested object. The method has been verified by preliminary experimental results on phantom. The result showed that the method can effectively reduce the scatter artifacts, increase the image contrast and increase the quality of the reconstructed slice image. This method is computationally efficient and easy to implement without the loss of real-time imaging capabilities.
The SLC25A47 locus controls gluconeogenesis and energy expenditure

Significance Given the impenetrable nature of the mitochondrial inner-membrane, most of the known metabolite carrier proteins, including SLC25A family members, are ubiquitously expressed in mammalian tissues. One exception is SLC25A47, which is selectively expressed in the liver. The present study showed that depletion of SLC25A47 reduced mitochondrial pyruvate flux and hepatic gluconeogenesis under a fasted state, while activating energy expenditure. The present work offers a liver-specific target through which we can restrict hepatic gluconeogenesis, which is often in excess under hyperglycemic and diabetic conditions.
Influence of Lithium- and Zinc-Containing Bioactive Glasses on Pulpal Regeneration

Abstract Objective To evaluate the potential of modified bioactive glasses containing lithium and zinc as pulp capping materials by investigating the odontogenic differentiation and mineralization response in the tooth culture model. Materials and Methods Lithium- and zinc-containing bioactive glasses (45S5.1Li, 45S5.5Li, 45S5.1Zn, 45S5.5Zn, 45S5.1Zn sol-gel, and 45S5.5Zn sol-gel), fibrinogen-thrombin, and biodentine were prepared to assess Axin2 gene expression at 0, 30 minutes, 1 hour, 12 hours, and 1 day and DSPP gene expression at 0, 3, 7, and 14 days in stem cells from human exfoliated deciduous teeth (SHEDs) using qRT-PCR. The experimental bioactive glasses incorporated with fibrinogen-thrombin and biodentine were placed on the pulpal tissue in the tooth culture model. Histology and immunohistochemistry were analyzed at 2 weeks and 4 weeks. Results Axin2 gene expression for all experimental groups was significantly higher than the control at 12 hours. The DSPP gene expression for all experimental groups was significantly higher than the control at 14 days. The presence of mineralization foci was significantly higher at 4 weeks for the modified bioactive glasses 45S5.5Zn, 45S5.1Zn sol-gel, and 45S5.5Zn sol-gel as well as Biodentine compared with the fibrinogen-thrombin control. Conclusion Lithium - and zinc - containing bioactive glasses increased Axin2 and DSPP gene expression in SHEDs and can potentially enhance pulp mineralization and regeneration. Zinc - containing bioactive glasses are a promising candidate to be used as pulp capping materials.
“It was like you were being literally punished for getting sick”: formerly incarcerated people’s perspectives on liberty restrictions during COVID-19

Abstract Background COVID-19 has greatly impacted the health of incarcerated individuals in the US. The goal of this study was to examine perspectives of recently incarcerated individuals on greater restrictions on liberty to mitigate COVID-19 transmission. Methods We conducted semi-structured phone interviews from August through October 2021 with 21 people who had been incarcerated in Bureau of Prisons (BOP) facilities during the pandemic. Transcripts were coded and analyzed, using a thematic analysis approach. Results Many facilities implemented universal “lockdowns,” with time out of the cell often limited to one hour per day, with participants reporting not being able to meet all essential needs such as showers and calling loved ones. Several study participants reported that repurposed spaces and tents created for quarantine and isolation provided “unlivable conditions. ” Participants reported receiving no medical attention while in isolation, and staff using spaces designated for disciplinary purposes (e.g., solitary housing units) for public health isolation purposes. This resulted in the conflation of isolation and discipline, which discouraged symptom reporting. Some participants felt guilty over potentially causing another lockdown by not reporting their symptoms. Programming was frequently stopped or curtailed and communication with the outside was limited. Some participants relayed that staff threatened to punish noncompliance with masking and testing. Liberty restrictions were purportedly rationalized by staff with the idea that incarcerated people should not expect freedoms, while those incarcerated blamed staff for bringing COVID-19 into the facility. Conclusions Our results highlighted how actions by staff and administrators decreased the legitimacy of the facilities’ COVID-19 response and were sometimes counterproductive. Legitimacy is key in building trust and obtaining cooperation with otherwise unpleasant but necessary restrictive measures. To prepare for future outbreaks facilities must consider the impact of liberty-restricting decisions on residents and build legitimacy for these decisions by communicating justifications to the extent possible.
Subparsec Clumping in the Nearby Molecular Cloud MBM 12

At a distance of 65 pc, the molecular cloud MBM 12 is the nearest molecular complex known. Results of extensive molecular and preliminary atomic spectral mapping of the MBM 12 complex are reported. The total H2 mass of the cloud is estimated to be about 30 solar masses. Although there are over 50 distinct emission clumps and the (C-13)O (J = 1-0) maps show structure within the MBM 12 complex down to the resolution limit of about 6500 AU. The large line widths may reflect either the evaporation of the clumps by the ambient hot gas or the presence of an ensemble of blended emission clumps that are smaller than the resolution limit. Preliminary results show H I envelopes about the molecular cores with column densities consistent with that expected for atomic to molecular transition regions. The kinematics of the MBM 12 complex imply kinetic energies of about 10 to the 45th ergs. This energy is typical of that produced by a bipolar flow from a young stellar object. 30 refs.
Deoxyschizandrin ameliorates obesity and non‐alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein‐coupled bile acid receptor 1 activation and leptin sensitization

Natural dual farnesyl X receptor (FXR)/G protein‐coupled bile acid receptor 1 (TGR5) activators have received little attention in the management of metabolic diseases. Deoxyschizandrin (DS), a natural lignan, occurs in S. chinensis fruit and has potent hepatoprotective effects, whereas its protective roles and mechanisms against obesity and non‐alcoholic fatty liver disease (NAFLD) are largely elusive. Here, we identified DS as a dual FXR/TGR5 agonist using luciferase reporter and cyclic adenosine monophosphate (cAMP) assays. DS was orally or intracerebroventricularly administrated to high‐fat diet‐induced obesity (DIO) mice, and methionine and choline‐deficient L‐amino acid diet (MCD diet)‐induced non‐alcoholic steatohepatitis to evaluate its protective effects. Exogenous leptin treatment was employed to investigate the sensitization effect of DS on leptin. The molecular mechanism of DS was explored by Western blot, quantitative real‐time PCR analysis, and ELISA. The results showed that DS activated FXR/TGR5 signaling and effectively reduced NAFLD in DIO and MCD diet‐fed mice. DS countered obesity in DIO mice by promoting anorexia and energy expenditure and reversing leptin resistance, involving both peripheral and central TGR5 activation and leptin sensitization. Our findings indicate that DS may be a novel therapeutic approach for alleviating obesity and NAFLD through regulating FXR and TGR5 activities and leptin signaling.
Linear regression analysis

Description: Regression analysis is an often used tool in the statistician's toolbox. This new edition takes into serious consideration the furthering development of regression computer programs that are efficient, accurate, and considered an important part of statistical research. The book provides up-to-date accounts of computational methods and algorithms currently in use without getting entrenched in minor computing details.
Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti‐HCoV‐229E Effects and Inhibitory Activity against LPS‐Induced Inflammation

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave‐assisted hydro‐distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD‐EO and MAHD‐EO (40.84 and 40.04 %, respectively); while in HD‐EO it only represented 15.36 %. The SD‐EO showed a strong antiviral activity against HCoV‐229E with IC50 of 10.93 μg/mL, whereas, MAHD‐EO and HD‐EO showed a moderate activity with IC50 values of 119.9 and 148.2 μg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3‐CL (pro). Moreover, the three EOs (50 μg/mL) decreased the levels of NO, IL‐6 and TNF‐α and suppressed IL‐6 and TNF‐α gene expression in LPS‐induced inflammation model in RAW264.7 macrophage cell lines.
Errata to 'An invariant of basic sets of Smale flows'

There is an error in [ 5], which is repeated in [ 6, 7] and [4, Definition 5.2. 5]. The problem is with the definition ofribbon sets. With the new definition given below all results are preserved. Ribbon sets were defined as the local stable manifold of a basic set of saddle type in a Smale flow. However, every local stable manifold has some ‘thickness’, > 0. But in the proof of Lemma 4.3, which is used to prove Theorem 4.1, one must be able to make arbitrarily many refinements and reorderings of the Markov partition. Hence a local stable manifold need not be invariant. Intuitively, what is needed is an infinitesimal stable manifold. Formally, we redefine a ribbon set to be the suspension of a disjoint union of local stable manifolds of points in a cross section of the basic set.
Population Pharmacokinetic Analysis of Rifampicin in Plasma, Cerebrospinal Fluid, and Brain Extracellular Fluid in South African Children with Tuberculous Meningitis

Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). ABSTRACT Limited knowledge is available on the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue, which is the site of infection. In this analysis, we characterize the distribution of rifampicin in cerebrospinal fluid (CSF), lumbar (LCSF) and ventricular (VCSF), and brain extracellular fluid (ECF). Children with TBM were included in this pharmacokinetic analysis. Sparse plasma, LCSF, and VCSF samples were collected opportunistically, as clinically indicated. Brain ECF was sampled using microdialysis (MD). Rifampicin was quantified with liquid chromatography with tandem mass spectrometry in all samples, and 25-desacetyl rifampicin in the plasma samples. The data were interpreted with nonlinear mixed-effects modeling, with the CSF and brain ECF modeled as “effect compartments. ” Data were available from 61 children, with median (min-max) age of 2 (0.3 to 10) years and weight of 11.0 (4.8 to 49.0) kg. A one-compartment model for parent and metabolite with first-order absorption and elimination via saturable hepatic clearance described the data well. Allometric scaling, maturation, and auto-induction of clearance were included. The pseudopartition coefficient between plasma and LCSF/VCSF was ~5%, while the value for ECF was only ~0.5%, possibly reflecting low recovery of rifampicin using MD. The equilibration half-life between plasma and LCSF/VCSF was ~4 h and between plasma and ECF ~2 h. Our study confirms previous reports showing that rifampicin concentrations in the LCSF are lower than in plasma and provides novel knowledge about rifampicin in the VCSF and the brain tissue. Despite MD being semiquantitative because the relative recovery cannot be quantified, our study presents a proof-of-concept that rifampicin reaches the brain tissue and that MD is an attractive technique to study site-of-disease pharmacokinetics in TBM.
DJ-1 Molecular Chaperone Activity Depresses Tau Aggregation Propensity through Interaction with Monomers

Tau aggregate-bearing lesions are pathological markers and potential mediators of tauopathic neurodegenerative diseases, including Alzheimer’s disease. The molecular chaperone DJ-1 colocalizes with tau pathology in these disorders, but it has been unclear what functional link exists between them. In this study, we examined the consequences of tau/DJ-1 interaction as isolated proteins in vitro. When added to full-length 2N4R tau under aggregation-promoting conditions, DJ-1 inhibited both the rate and extent of filament formation in a concentration-dependent manner. Inhibitory activity was low affinity, did not require ATP, and was not affected by substituting oxidation incompetent missense mutation C106A for wild-type DJ-1. In contrast, missense mutations previously linked to familial Parkinson’s disease and loss of α-synuclein chaperone activity, M26I and E64D, displayed diminished tau chaperone activity relative to wild-type DJ-1. Although DJ-1 directly bound the isolated microtubule-binding repeat region of tau protein, exposure of preformed tau seeds to DJ-1 did not diminish seeding activity in a biosensor cell model. These data reveal DJ-1 to be a holdase chaperone capable of engaging tau as a client in addition to α-synuclein. Our findings support a role for DJ-1 as part of an endogenous defense against the aggregation of these intrinsically disordered proteins.
The Impaired Wound Healing Process Is a Major Factor in Remodeling of the Corneal Epithelium in Adult and Adolescent Patients With Keratoconus

Purpose Keratoconus (KTCN) is the most common corneal ectasia, characterized by pathological cone formation. Here, to provide an insight into the remodeling of the corneal epithelium (CE) during the course of the disease, we evaluated topographic regions of the CE of adult and adolescent patients with KTCN. Methods The CE samples from 17 adult and 6 adolescent patients with KTCN, and 5 control CE samples were obtained during the CXL and PRK procedures, respectively. Three topographic regions, central, middle, and peripheral, were separated toward RNA sequencing and MALDI-TOF/TOF Tandem Mass Spectrometry. Data from transcriptomic and proteomic investigations were consolidated with the morphological and clinical findings. Results The critical elements of the wound healing process, epithelial–mesenchymal transition, cell–cell communications, and cell–extracellular matrix interactions were altered in the particular corneal topographic regions. Abnormalities in pathways of neutrophils degranulation, extracellular matrix processing, apical junctions, IL, and IFN signaling were revealed to cooperatively disorganize the epithelial healing. Deregulation of the epithelial healing, G2M checkpoints, apoptosis, and DNA repair pathways in the middle CE topographic region in KTCN explains the presence of morphological changes in the corresponding doughnut pattern (a thin cone center surrounded by a thickened annulus). Despite similar morphological characteristics of CE samples in adolescents and adults with KTCN, their transcriptomic features were different. Values of the posterior corneal elevation differentiated adults with KTCN from adolescents with KTCN and correlated with the expression of TCHP, SPATA13, CNOT3, WNK1, TGFB2, and KRT12 genes. Conclusions Identified molecular, morphological, and clinical features indicate the effect of impaired wound healing on corneal remodeling in KTCN CE.
HPV‐induced host epigenetic reprogramming is lost upon progression to high‐grade cervical intraepithelial neoplasia

The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV‐induced host epigenome‐wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease‐free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)‐HPV, a signature reflective of changes in the healthy host epigenome related to high‐risk HPV strains (AUC = 0.78, 95% CI: 0.72‐0.85, in nondiseased women). Looking at HPV‐associated changes across disease development, HPV‐infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID‐HPV index, indicating the WID‐HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID‐HPV is positively associated with apoptosis (ρ = 0.48; P < .001) and negatively associated with epigenetic replicative age (ρ = −0.43; P < .001). Taken together, our data suggest the WID‐HPV captures a clearance response associated with apoptosis of HPV‐infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer.