Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of ribonuclease Y in pilus production by M49 Streptococcus pyogenes strain via modulation of messenger RNA level of transcriptional regulator

Streptococcus pyogenes displays a wide variety of pili, which is largely dependent on serotype. A distinct subset of S. pyogenes strains that possess the Nra transcriptional regulator demonstrates thermoregulated pilus production. Findings obtained in the present study of an Nra‐positive serotype M49 strain revealed involvement of conserved virulence factor A (CvfA), also referred to as ribonuclease Y (RNase Y), in virulence factor expression and pilus production, while a cvfA deletion strain showed reduced pilus production and adherence to human keratinocytes as compared with wild‐type and revertant strains. Furthermore, transcript levels of pilus subunits and srtC2 genes were decreased by cvfA deletion, which was remarkable at 25°C. Likewise, both messenger RNA (mRNA) and protein levels of Nra were remarkably decreased by cvfA deletion. Whether the expression of other pilus‐related regulators, including fasX and CovR, was subject to thermoregulation was also examined. While the mRNA level of fasX, which inhibits cpa and fctA translation, was decreased by cvfA deletion at both 37°C and 25°C, CovR mRNA and protein levels, as well as its phosphorylation level were not significantly changed, suggesting that neither fasX nor CovR is necessarily involved in thermosensitive pilus production. Phenotypic analysis of the mutant strains revealed that culture temperature and cvfA deletion had varied effects on streptolysin S and SpeB activities. Furthermore, bactericidal assay data showed that cvfA deletion decreased the rate of survival in human blood. Together, the present findings indicate that CvfA is involved in regulation of pilus production and virulence‐related phenotypes of the serotype M49 strain of S. pyogenes.
Magnetization of a Mesoscopic Superconducting Sr2RuO4 Plate on Micro-dc-SQUIDs

We report on the measurement of the magnetization of mesoscopic plates made of the chiral p-wave superconductor Sr2RuO4 by using micro-dc-superconducting quantum interference devices (SQUIDs) positioned immediately below the plates. The high sensitivity of the micro-dc-SQUIDs is expected to enable the detection of direction of the chirality. We measured the magnetization of mesoscopic Sr2RuO4 plate-like crystals and found residual magnetization at the zero external field in the thin sample and detected a first critical field Hc1 symmetric against the magnetic field direction. The observed symmetric first critical field Hc1 is consistent with the formation of multi-chiral domain structures. We carefully discuss the origin of the residual magnetization and conclude that it is due to the remnant vortices rather than the chiral edge current.
Dynamics of stratified turbulence decaying from a high buoyancy Reynolds number

We present direct numerical simulations (DNS) of unforced stratified turbulence with the objective of testing the strongly stratified turbulence theory. According to this theory the characteristic vertical scale of the turbulence is given by $\ell _{v}\sim u_{h}/N$ , where $u_{h}$ is the horizontal velocity scale and $N$ the Brunt–Väisälä frequency. Combined with the hypothesis of the energy dissipation rate scaling as ${\it\epsilon}\sim u_{h}^{3}/\ell _{h}$ , this theory predicts inertial range scalings for the horizontal spectrum of horizontal kinetic energy and of potential energy, according to $E(k_{h})\propto k_{h}^{-5/3}$ . We begin by presenting a scaling analysis of the horizontal vorticity equation from which we recover the result regarding the vertical scale, $\ell _{v}\sim u_{h}/N$ , highlighting in the process the important dynamical role of large-scale vertical shear of horizontal velocity. We then present the results from decaying DNS, which show a good agreement with aspects of the theory. In particular, the vertical Froude number is found to reach a constant plateau in time, of the form $Fr_{v}=u_{h}/(N\ell _{v})=C$ with $C=O(1)$ in all the runs. The derivation of the dissipation scaling ${\it\epsilon}\sim u_{h}^{3}/\ell _{h}$ at low Reynolds number in the context of decaying stratified turbulence highlights that the same scaling holds at high $\mathscr{R}=ReFr_{h}^{2}\gg 1$ as well as at low $\mathscr{R}\ll 1$ , which is known (see Brethouwer et al., J. Fluid Mech., vol. 585, 2007, pp. 343–368) but not sufficiently emphasized in recent literature. We find evidence in our DNS of the dissipation scaling holding at $\mathscr{R}=O(1)$ , which we interpret as being in the viscous regime. We also find ${\it\epsilon}_{k}\sim u_{h}^{3}/\ell _{h}$ and ${\it\epsilon}_{p}\sim u_{h}^{3}/\ell _{h}$ (with ${\it\epsilon}={\it\epsilon}_{k}+{\it\epsilon}_{p}$ ), in our high-resolution run at earlier times corresponding to $\mathscr{R}=O(10)$ , which is in the transition between the strongly stratified and the viscous regimes. The horizontal spectrum of horizontal kinetic energy collapses in time using the scaling $E_{h}(k_{h})=C_{1}{\it\epsilon}_{k}^{2/3}k_{h}^{-5/3}$ and the horizontal potential energy spectrum is well described by $E_{p}(k_{h})=C_{2}{\it\epsilon}_{p}{\it\epsilon}_{k}^{-1/3}k_{h}^{-5/3}$ . The presence of an inertial range in the horizontal direction is confirmed by the constancy of the energy flux spectrum over narrow ranges of $k_{h}$ . However, the vertical energy spectrum is found to differ significantly from the expected $E_{h}(k_{v})\sim N^{2}k_{v}^{-3}$ scaling, showing that $Fr_{v}$ is not of order unity on a scale-by-scale basis, thus providing motivation for further investigation of the vertical structure of stratified turbulence.
A nested case‐control study of untargeted albumin adductomics and acute myeloid leukemia

Environmental exposures often produce reactive electrophiles in vivo, leading to oxidative stress, which plays a major role in carcinogenesis. These electrophiles frequently form adducts with human albumin, which can be measured to assess in vivo oxidative stress. Here, we aimed to examine the associations between circulatory albumin adducts and acute myeloid leukemia (AML), the most common adult myeloid leukemia that showed consistent associations with environmental exposures. We conducted a nested case‐control study of 52 incident AML cases and 103 controls matched on age, sex and race within two prospective cohorts: the CLUE and PLCO studies. We measured 42 untargeted albumin adducts in prediagnostic samples using liquid chromatography‐high‐resolution mass spectrometry. Circulatory albumin adducts were associated with AML in conditional logistic regression models. For instance, higher levels of Cys34 disulfide adduct of the S‐γ‐glutamylcysteine, a precursor of the essential antioxidant, glutathione were associated with a lower risk of AML (odds ratios [95% confidence intervals]) for the 1st, 2nd and 3rd tertiles were 1.0, 0.65 (0.31‐1.36) and 0.31 (0.12‐0.80), respectively (P‐trend = .01). These associations were largely driven by effects present among cases diagnosed at or above the median follow‐up time of 5.5 years. In conclusion, applying a novel approach to characterize exposures in the prediagnostic samples, we found evidence supporting the notion that oxidative stress may play a role in the pathogenesis of AML. Our findings offer insight into AML etiology and may be relevant in identifying novel therapeutic targets.
Effects of Season and Daylight Saving Time Shifts on Sleep Symptoms

Background and Objectives There has been conflicting evidence regarding the association between seasonal changes and daylight saving time (DST) and sleep disorders. This topic is of particular interest currently because the United States and Canada are considering the elimination of seasonal clock changes. The aim of this study was to compare sleep symptoms among participants who were interviewed in different seasons and before/after the transition into DST and standard time (ST). Methods A total of 30,097 people aged 45–85 years taking part in the Canadian Longitudinal Study on Aging were studied. Participants completed a questionnaire on sleep duration, satisfaction, sleep-onset insomnia, sleep-maintenance insomnia, and hypersomnolence symptoms. Sleep disorders were compared between participants who were interviewed during different seasons and at different times of the year (DST/ST). Data were analyzed using χ2, analysis of variance, binary logistic, and linear regression tests. Results Among participants interviewed in different seasons, we found no difference in dissatisfaction with sleep, sleep onset, sleep maintenance, and hypersomnolence. Those interviewed in summer had slightly shorter sleep duration compared with those in winter (6.76 ± 1.2 vs 6.84 ± 1.3 hours). Participants interviewed 1 week before vs 1 week after DST transition showed no difference in sleep symptoms, except for a 9-minute decrease in sleep duration a week after transition. However, those who were interviewed a week after transition to ST compared with a week before reported more dissatisfaction with sleep (28% vs 22.6%, adjusted odds ratio [aOR] 1.34, 95% CI 1.02–1.76), higher sleep-onset insomnia (7.1% vs 3.3%, aOR 2.26, 95% CI 1.19–4.27), higher sleep-maintenance insomnia (12.9% vs 8.2%, aOR 1.64, 95% CI 1.02–2.66), and more hypersomnolence with adequate sleep (7.3% vs 3.6%, aOR 2.08, 95% CI 1.14–3.79). Discussion We found small seasonal variations in sleep duration but no difference in other sleep symptoms. The transition from DST to ST was associated with a transient increase in sleep disorders.
The Validity of the Frozen-in Condition for the Inner Magnetosphere

Single fluid magnetohydrodynamics (MHD) uses the frozen-in condition to determine the electric field from the plasma flow velocity. The curl of this electric field is in turn used in Faraday’s law to determine the time rate of change of the magnetic field. Within the MHD context the portion of the electric field given by a scalar potential is not important. However, models such as the Rice Convection Model (RCM) usually require the electric potential be specified as a boundary condition. Here we explore the validity of the frozen-in condition and show that within the MHD context, the frozen-in condition is valid provided the flows are barotropic, with the pressure gradient parallel to the density gradient. This is equivalent to isentropic flows. But simulations using the OpenGGCM model at the Community Coordinated Modeling Center show that the flow need not be barotropic. This suggests anomalous processes, such as reconnection, introduce density and pressure gradients that are not aligned. How much this changes the frozen-in condition is an open question, as it is a second-order effect. Nevertheless, this analysis emphasizes that the issue in merging the MHD and drift models may in part be associated with the fact that the potential electric field is not well constrained by the ideal frozen-in condition, with only the induction electric field being required to close the MHD equations. The next approximation is the frozen-in electron condition, which effectively assumes that the electron thermal pressure can be ignored, and this may provide a useful means for mapping MHD-derived electric fields to the drift domain.
Nonlinear state-dependent impulsive system in fed-batch culture and its optimal control

In fed-batch culture, feeding substrates is to provide sufficient nutrition and reduce inhibitions simultaneously for cells growth. Hence, when and how much to feed substrates are important during the process. In this paper, a nonlinear impulsive controlls system, in which the volume of feeding is taken as the control function, is proposed to formulate the fed-batch fermentation process.In the system, both impulsive moments and jumps size of state are state-dependent. Some important properties of the system are investigated. To maximize the concentration of target product at the terminal time, an optimal control model involving the nonlinear state-dependent impulsive controlled system is presented.The optimal control problem is subject to the continuous state inequality constraint and the control constraint. The existence of optimal control is also obtained. In order to derive the optimality conditions, the optimal control model is transcribed into an equivalent one by treating the constraints. Finally, the optimality conditions of the optimal control model are obtained via calculus of variations.
Termination of STING responses is mediated via ESCRT‐dependent degradation

cGAS‐STING signalling is induced by detection of foreign or mislocalised host double‐stranded (ds)DNA within the cytosol. STING acts as the major signalling hub, where it controls production of type I interferons and inflammatory cytokines. Basally, STING resides on the ER membrane. Following activation STING traffics to the Golgi to initiate downstream signalling and subsequently to endolysosomal compartments for degradation and termination of signalling. While STING is known to be degraded within lysosomes, the mechanisms controlling its delivery remain poorly defined. Here we utilised a proteomics‐based approach to assess phosphorylation changes in primary murine macrophages following STING activation. This identified numerous phosphorylation events in proteins involved in intracellular and vesicular transport. We utilised high‐temporal microscopy to track STING vesicular transport in live macrophages. We subsequently identified that the endosomal complexes required for transport (ESCRT) pathway detects ubiquitinated STING on vesicles, which facilitates the degradation of STING in murine macrophages. Disruption of ESCRT functionality greatly enhanced STING signalling and cytokine production, thus characterising a mechanism controlling effective termination of STING signalling.
Effects of dynamization timing and degree on bone healing of different fracture types

Dynamization, that is, increasing interfragmentary movement (IFM) by reducing fixation stiffness from a rigid to a more flexible state, has been successfully used in clinical practice to promote fracture healing. However, it remains unclear how dynamization timing and degree affect bone healing of different fracture types. Finite element models of tibial fractures based on the OTA/AO classification (Simple: A1‐Spiral, A2‐Oblique, A3‐Transverse; Wedge: B2‐Spiral, B3‐Fragmented; Complex: C2‐Segment, C3‐Irregular), in combination with fuzzy logic‐based mechano‐regulatory tissue differentiation algorithms, were used to simulate the healing process when dynamization of varied degrees (dynamization coefficient or DC = 0‐0.9; 0.9 represents 90% reduction in the fixation stiffness relative to a rigid fixation) were applied at different time points after fracture. The fuzzy logic‐based algorithms have been validated with a preclinical animal model. The results showed that the healing responses of type A fractures were more sensitive to the changes in dynamization degree and timing comparing with type B or C fractures. Additionally, the optimal dynamization regime for each fracture type was different. For type A fractures, a moderate dynamization degree (e.g., DC = 0.5) applied after Week 1 promoted the recovery of biomechanical integrity. For type B and C fractures, the effective dynamization included a greater dynamization degree (DC = 0.7) applied after Week 2. Our results further demonstrated that the fracture morphology affected interfragmentary strain environments within the callus, leading to varied healing results for different fracture types. These results suggest that the effects of dynamization are highly dependent of the fracture types. Therefore, specific dynamization strategies should be chosen for different fracture types to achieve optimal healing outcomes.
2-D isotropic negative refractive index in a N-type four-level atomic system

Abstract 2-D(Two-dimensional) isotropic negative refractive index (NRI) is explicitly realized via the orthogonal signal and coupling standing-wave fields coupling the Ntype four-level atomic system. Under some key parameters of the dense vapour media, the atomic system exhibits isotropic NRI with simultaneous negative permittivity and permeability (i.e. left-handedness) in the 2-D x-y plane. Compared with other 2-D NRI schemes, the coherent atomic vapour media in our scheme may be an ideal 2-D isotropic NRI candidate and has some potential advantages, significance or applications in the further investigation.
Representative Rodent Models for Renal Transporter Alterations in Human Nonalcoholic Steatohepatitis

Alterations in renal elimination processes of glomerular filtration and active tubular secretion by renal transporters can result in adverse drug reactions. Nonalcoholic steatohepatitis (NASH) alters hepatic transporter expression and xenobiotic elimination, but until recently, renal transporter alterations in NASH were unknown. This study investigates renal transporter changes in rodent models of NASH to identify a model that recapitulates human alterations. Quantitative protein expression by surrogate peptide liquid chromatography-coupled mass spectrometry (LC-MS/MS) on renal biopsies from NASH patients was used for concordance analysis with rodent models, including methionine/choline deficient (MCD), atherogenic (Athero), or control rats and Leprdb/db MCD (db/db), C57BL/6J fast-food thioacetamide (FFDTH), American lifestyle-induced obesity syndrome (ALIOS), or control mice. Demonstrating clinical similarity to NASH patients, db/db, FFDTH, and ALIOS showed decreases in glomerular filtration rate (GFR) by 76%, 28%, and 24%. Organic anion transporter 3 (OAT3) showed an upward trend in all models except the FFDTH (from 3.20 to 2.39 pmol/mg protein), making the latter the only model to represent human OAT3 changes. OAT5, a functional ortholog of human OAT4, significantly decreased in db/db, FFDTH, and ALIOS (from 4.59 to 0.45, 1.59, and 2.83 pmol/mg protein, respectively) but significantly increased for MCD (1.67 to 4.17 pmol/mg protein), suggesting that the mouse models are comparable to human for these specific transport processes. These data suggest that variations in rodent renal transporter expression are elicited by NASH, and the concordance analysis enables appropriate model selection for future pharmacokinetic studies based on transporter specificity. These models provide a valuable resource to extrapolate the consequences of human variability in renal drug elimination. SIGNIFICANCE STATEMENT Rodent models of nonalcoholic steatohepatitis that recapitulate human renal transporter alterations are identified for future transporter-specific pharmacokinetic studies to facilitate the prevention of adverse drug reactions due to human variability.
Investigation of a Jacobian-free Newton-Krylov solution to multiphase flows

The current study is focused on investigating a Jacobian-Free Newton-Krylov (JFNK) method to obtain a fully-implicit solution for two phase flows. In the JFNK formulation, the Jacobian matrix is not directly determined potentially leading to major computational savings compared to a simple Newton’s solver. Prior to the implementation of JFNK to solve two-phase flow problem, it is utilized to solve the governing equations corresponding to single phase flow. The objectives of the present study are (i) Application of the JFNK method to two-fluid models, (ii) Investigation of the advantages and disadvantages of the method compared to commonly used explicit methods, and (iii) Comparison of the numerical predictions with those obtained by the current version of the Network thermalhydraulics code, CATHENA. The background information required is presented and the numerical setup for each test case is discussed in detail. Three well-known benchmarks are considered, the 1D dam break problem, the water faucet and the oscillating manometer. For single phase flow simulations, the Shallow Water Wave Equations is selected to model the motion of the fluid and a backward Euler scheme is utilized for the temporal discretization along with a central-upwind Godonuv scheme for the spatial discretization. For the two-phase simulations, an isentropic (four equation) two fluid model is chosen. Time discretization is performed by a backward Euler scheme and the AUSM+ scheme is applied to the convective fluxes. The source terms are discretized using a central differencing scheme. For comparison, one explicit and two implicit formulations, one with Newton’s solver with the Jacobian matrix and one with JFNK, are implemented for each set of governing equations. A detailed grid and model parameter sensitivity analysis is performed to identify the advantages and disadvantages of JFNK for each case. For all three benchmarks, the JFNK predictions are in good agreement with the analytical solutions and explicit profiles. Further, stable results can be achieved using high CFL (CourantFriedrichsLewy ) numbers up to 100 with a suitable choice of JFNK parameters. The computational time is significantly reduced by JFNK compared to the calculations requiring the determination of the Jacobian matrix. This reduction is in the order of 80%.
Behavioural and environmental risk factors associated with primary schoolchildren’s overweight and obesity in urban Indonesia

Abstract Objectives: To aid the design of nutrition interventions in low- and middle-income countries undergoing a nutrition transition, this study examined behavioural and environmental risk factors associated with childhood overweight and obesity in urban Indonesia. Design: Body height and weight of children were measured to determine BMI-for-age Z-scores and childhood overweight and obesity status. A self-administered parental survey measured socio-economic background, children’s diet, physical activity, screen time and parental practices. Logistic and quantile regression models were used to assess the association between risk factors and the BMI-for-age Z-score distribution. Setting: Public primary schools in Central Jakarta, sampled at random. Participants: Children (n 1674) aged 6–13 years from 18 public primary schools. Results: Among the children, 31·0 % were overweight or obese. The prevalence of obesity was higher in boys (21·0 %) than in girls (12·0 %). Male sex and height (aOR = 1·67; 95 % CI 1·30, 2·14 and aOR = 1·16; 95 % CI 1·14, 1·18, respectively) increased the odds of being overweight or obese, while the odds reduced with every year of age (aOR = 0·43; 95 % CI 0·37, 0·50). Maternal education was positively associated with children’s BMI at the median of the Z-score distribution (P = 0·026). Dietary and physical activity risk scores were not associated with children’s BMI at any quantile. The obesogenic home food environment score was significantly and positively associated with the BMI-for-age Z-score at the 75th and 90th percentiles (P = 0·022 and 0·023, respectively). Conclusions: This study illustrated the demographic, behavioural and environmental risk factors for overweight and obesity among primary schoolchildren in a middle-income country. To foster healthy behaviours in primary schoolchildren, parents need to ensure a positive home food environment. Future sex-responsive interventions should involve both parents and children, promote healthy diets and physical activity and improve food environments in homes and schools.