Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing of SbPPCK1-3 Negatively Affects Development, Stress Responses and Productivity in Sorghum

Phosphoenolpyruvate carboxylase (PEPC) plays central roles in photosynthesis, respiration, amino acid synthesis, and seed development. PEPC is regulated by different post-translational modifications. Between them, the phosphorylation by PEPC-kinase (PEPCk) is widely documented. In this work, we simultaneously silenced the three sorghum genes encoding PEPCk (SbPPCK1-3) by RNAi interference, obtaining 12 independent transgenic lines (Ppck1-12 lines), showing different degrees of SbPPCK1-3 silencing. Among them, two T2 homozygous lines (Ppck-2 and Ppck-4) were selected for further evaluation. Expression of SbPPCK1 was reduced by 65% and 83% in Ppck-2 and Ppck-4 illuminated leaves, respectively. Expression of SbPPCK2 was higher in roots and decreased by 50% in Ppck-2 and Ppck-4 in this tissue. Expression of SbPPCK3 was low and highly variable. Despite the incomplete gene silencing, it decreased the degree of phosphorylation of PEPC in illuminated leaves, P-deficient plants, and NaCl-treated plants. Both leaves and seeds of Ppck lines had altered metabolic profiles and a general decrease in amino acid content. In addition, Ppck lines showed delayed flowering, and 20% of Ppck-4 plants did not produce flowers at all. The total amount of seeds was lowered by 50% and 36% in Ppck-2 and Ppck-4 lines, respectively. The quality of seeds was lower in Ppck lines: lower amino acid content, including Lys, and higher phytate content. These data confirm the relevance of the phosphorylation of PEPC in sorghum development, stress responses, yield, and quality of seeds.
Leveraging Real-World Evidence Derived from Patient Registries for Premarket Medical Device Regulatory Decision-Making

ABSTRACT In this era of “Big Data,” there are many sources of real-world healthcare data that could be leveraged in clinical research in the regulatory environment. While such large quantities of data reflect real-world clinical practice and may potentially be used to reduce the cost or time of conducting clinical research, challenges arise concerning using real-world evidence derived from real-world data to inform or support premarket regulatory decision-making for medical devices. This article discusses such opportunities and challenges from statistical and regulatory perspectives with an emphasis on the use of real-world evidence derived from high-quality national and international patient registries.
Short-Term Effects of Manual Therapy plus Capacitive and Resistive Electric Transfer Therapy in Individuals with Chronic Non-Specific Low Back Pain: A Randomized Clinical Trial Study

Background and Objectives: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Capacitive and resistive electric transfer (TECAR) therapy utilizes radiant energy to generate endogenous heat and is widely used for the treatment of chronic musculoskeletal pain. The aim of this study was to investigate the efficacy of manual therapy (MT) program combined with TECAR therapy in individuals with CNSLBP. Materials and Methods: Sixty adults with CNSLBP were randomly divided equally into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet, and the third group (control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 h with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland–Morris Disability Questionnaire (RMDQ), pressure pain threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both during the second week and the one-month follow-up (p < 0.001). Between-group differences were also noticed between the two intervention groups in the second week (p < 0.05). Differences in the RMDQ score were detected between the intervention groups and the control group in the second week and at the one-month follow-up (p < 0.001), while differences between the two intervention groups were only detected at the one-month follow-up (p < 0.001). Regarding the PPT values, differences were found mainly between the MT + TECAR group and the control group and between the MT + TECAR group and the MT group (p < 0.05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant at the one-month follow-up (p < 0.05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region at both time points compared to the control group without, however, statistically significant differences between them (p > 0.05). Conclusions: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in the mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.
Reduced skin permeation and penetration of clobetasol propionate when Dermovate cream is applied at short time intervals with emollients

Background: Dermovate cream containing 0.05% clobetasol propionate is a very potent topical corticosteroid (TCS) used in the treatment of severe inflammatory dermatoses. Regular emollient therapy should continue alongside clobetasol propionate treatment, however, the impact on drug delivery to the skin when both products are applied at similar times is unknown. Objectives: To assess whether application of emollients at similar times to Dermovate cream alter the delivery of clobetasol propionate to the skin. Methods: This study was conducted using ex vivo human skin mounted in Franz cells. Dermovate cream was applied before or after three different emollients, Hydromol Intensive cream, Doublebase gel, and Diprobase ointment at 5 ‐ or 30 ‐ min intervals. Drug delivery to the skin was assessed up to 24 h using high ‐ performance liquid chromatography. Results: Significantly reduced clobetasol propionate delivery to the skin was observed when Dermovate cream was applied either before or after the three different emollients, compared to the application of Dermovate cream alone. The data suggest in situ formation of a mixed Dermovate cream and emollient layer which reduces clobetasol
The Blood Concentration of Metallic Nanoparticles Is Related to Cognitive Performance in People with Multiple Sclerosis: An Exploratory Analysis

The imbalance in the concentration of metallic nanoparticles has been demonstrated to play an important role in multiple sclerosis (MS), which may impact cognition. Biomarkers are needed to provide insights into the pathogenesis and diagnosis of MS. They can be used to gain a better understanding of cognitive decline in people with MS (pwMS). In this study, we investigated the relationship between the blood concentration of metallic nanoparticles (blood nanoparticles) and cognitive performance in pwMS. First, four mL blood samples, clinical characteristics, and cognitive performance were obtained from 21 pwMS. All participants had relapse–remitting MS, with a score of ≤4.5 points in the expanded disability status scale. They were relapse-free in the three previous months from the day of collection and had no orthopedic, muscular, cardiac, and cerebellar diseases. We quantified the following metallic nanoparticles: aluminum, chromium, copper, iron, magnesium, nickel, zinc, and total concentration. Cognitive performance was measured by mini-mental state examination (MMSE) and the symbol digit modalities test (SDMT). Pearson’s and Spearman’s correlation coefficients and stepwise linear regression were calculated to assess the relationship between cognitive performance and blood nanoparticles. We found that better performance in SDMT and MMSE was related to higher total blood nanoparticles (r = 0.40; p < 0.05). Also, better performance in cognitive processing speed and attention (SDMT) and mental state (MMSE) were related to higher blood iron (r = 0.44; p < 0.03) and zinc concentrations (r = 0.41; p < 0.05), respectively. The other metallic nanoparticles (aluminum, chromium, copper, magnesium, and nickel) did not show a significant relationship with the cognitive parameters (p > 0.05). Linear regression estimated a significant association between blood iron concentration and SDMT performance. In conclusion, blood nanoparticles are related to cognitive performance in pwMS. Our findings suggest that the blood concentration of metallic nanoparticles, particularly the iron concentration, is a promising biomarker for monitoring cognitive impairment in pwMS.
Conservative magnetic moment of runaway electrons and collisionless pitch-angle scattering

Recently, the validity of the guiding-center approach to model relativistic runaway electrons in tokamaks has been challenged by full-orbit simulations that demonstrate the breakdown of the standard magnetic moment conservation. In this paper, we derive a new expression for the magnetic moment of relativistic runaway electrons with , which is conserved significantly better than the standard one. The new result includes one of the second-order corrections in the standard guiding-center theory which, in case of runaway electrons with , can peculiarly be of the same order as the lowest-order term. The better conservation of the new magnetic moment also explains the collisionless pitch-angle-scattering effect observed in full-orbit simulations since it allows momentum transfer between the perpendicular and parallel directions when the runaway electron is accelerated by an electric field. While the derivation of the second-order correction to the magnetic moment in general case would require the full extent of the relativistic second-order guiding-center theory, we exploit the Lie-perturbation method at the limit which simplifies the computations significantly. Consequently, we present the corresponding guiding-center equations applicable to runaway electrons.
Understanding the Impact of Quantitative Decision-Making on Engineering Managers

As an engineering manager, it is important to focus on employee productivity to provide the best output or product. Furthermore, an engineering manager must exemplify leadership skills, rather than mostly focusing on the business side of things as an engineer. Primarily, a manager must know how to problem solve because this skill is crucial to a business' success. There are plenty of methods and strategies to yield the best decision, but some are better than others. This article uses real-life examples to demonstrate the importance of quantitative decision-making in engineering management. These examples show how some decisions can be subject to error, as well. Project management requires many variables, concepts, and models for the best performance results. For practical application, this article can help provide some guidance and practices for engineering managers. This article highlights key factors to consider when using quantitative methods in engineering environments as well as effective quantitative methods that engineering managers can use in the field. This article highlights some of the common applications and pitfalls of different quantitative methods in engineering environment.
Discrete and continuous bivariate lifetime models in presence of cure rate: a comparative study under Bayesian approach

ABSTRACT The modeling and analysis of lifetime data in which the main endpoints are the times when an event of interest occurs is of great interest in medical studies. In these studies, it is common that two or more lifetimes associated with the same unit such as the times to deterioration levels or the times to reaction to a treatment in pairs of organs like lungs, kidneys, eyes or ears. In medical applications, it is also possible that a cure rate is present and needed to be modeled with lifetime data with long-term survivors. This paper presented a comparative study under a Bayesian approach among some existing continuous and discrete bivariate distributions such as the bivariate exponential distributions and the bivariate geometric distributions in presence of cure rate, censored data and covariates. In presence of lifetimes related to cured patients, it is assumed standard mixture cure rate models in the data analysis. The posterior summaries of interest are obtained using Markov Chain Monte Carlo methods. To illustrate the proposed methodology two real medical data sets are considered.
Discrimination of Sayamakaori and Yabukita Which Are Original Plant Source of Japanese Green Tea and Identification of Specific Compounds for the Former by Nuclear Magnetic Resonance Metabolomics Techniques Combined with Isolation by Chromatography Methods

Camellia sinensis leaves are one of the most economically important crops, and various tea cultivars are available in Japan. In the present study, we compared the constituents of Camellia sinensis var. sinensis cv. Yabukita (“Yabukita”), a standard tea cultivar, and those of C. sinensis var. sinensis cv. Sayamakaori (“Sayamakaori”), grown in Saitama Prefecture, using proton nuclear magnetic resonance (1H-NMR) metabolomics technology. Principal component analysis and hierarchical cluster analysis of 1H-NMR spectroscopic data of the MeOH extracts of C. sinensis leaves revealed differences in the metabolic profiles of each tea cultivar. Chromatographic separation based on 1H-NMR spectral data showed that kaempferol 3-O-β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside was a distinct component of “Sayamakaori”. This compound can be used as maker for the identification of “Sayamakaori” and the maintenance of its quality.
Adaptive phase locked loop in multi-standard frequency synthesizers /

The phase locked loop (PLL) based frequency synthesizer is an important com­ ponent in wireless transceivers to provide precise and fine-tunable local oscillation frequencies. Spectrum and timing specifications of various wireless standards impose stringent requirements on frequency synthesizer performance. The necessity of mono­ lithic integration makes frequency synthesizer design even more challenging because it involves both high frequency building blocks, such as VCO and prescaler, as well as low firequency filters and large amount of digital circuitry. Moreover, as multistandard frequency synthesizers are required for smooth migration and backward compatibility in the wireless standard evolution, hardware sharing and design reuse issues become critical for highly efficient design with fast time-to-market and first silicon success. In this dissertation, a top-down design and bottom-up verification flow is de­ veloped targeting the difliculties in the SPICE simulation of frequency synthesizers. The mixed-mode simulation methodology with the proposed switch macromodels and the VerilogA macromodels provides much faster speed and nearly the same accuracy compared with its all-transistor counterpart. An example of multistandard frequency synthesizers is studied, designed and im­ plemented for GSM and WCDMA modes. The hardware sharing issues are discussed in the proposed system architecture that makes the PFD, charge pump, loop filter, integer frequency divider and VCO all shared between the two modes, which is 70% ii of the entire synthesizer in term of die area. This is accomplished by applying frac­ tional frequency synthesis to the GSM mode and integer frequency synthesis to the WCDMA mode. A high-speed low power dual modulus prescaler is also proposed to operate up to 2.1GHz at 3.3V supply voltage with 11.6mW power consumption in 0.5;xm CMOS. For PLL frequency synthesizers, the loop bandwidth involves design tradeoffs be­ tween the lock time and spur level. The adaptive PLL has provided an excellent solution to this problem. In the conventional adaptive PLL, however, the loop band­ width enhancement in the speed-up mode is constrained to approximately 1/10 of the reference frequency for stability considerations. A novel adaptation scheme is pro­ posed that enables extended loop bandwidth enhancement by adaptively controlling the reference frequency and other loop parameters. In addition, the adjustable and programmable loop parameters in the adaptive PLL, such as the loop bandwidth, charge pump current and reference frequency, make it feasible to maximize hardware sharing in multistandard frequency synthesizers. The proposed adaptive frequency synthesizer is designed and implemented in 0.5^m CMOS at 450MHz frequency range. In the speed-up mode, the loop bandwidth is enhanced by 16 times, resulting in a fast settling time of 260^s to within 20kHz for a 72MHz frequency step.
A non‐linear model for censored and mismeasured time varying covariates in survival models, with applications in human immunodeficiency virus and acquired immune deficiency syndrome studies

In survival regression analysis, when the time‐dependent covariates are censored and measured with errors, a joint model is often considered for the longitudinal covariate data and the survival data. Typically, an empirical linear (mixed) model is assumed for the time‐dependent covariates. However, such an empirical linear covariate model may be inappropriate for the (unobserved) censored covariate values that may behave quite differently from the observed covariate process. In applications such as human immunodeficiency virus–acquired immune deficiency syndrome studies, a mechanistic non‐linear model can be derived for the covariate process on the basis of the underlying data generation mechanisms and such a non‐linear covariate model may provide better ‘predictions’ for the censored and mismeasured covariate values. We propose a joint Cox and non‐linear mixed effect model to model survival data with censored and mismeasured time varying covariates. We use likelihood methods for inference, implemented by the Monte Carlo EM algorithm. The models and methods are evaluated by simulations. An acquired immune deficiency syndrome data set is analysed in detail, where the time‐dependent covariate is a viral load which may be censored because of a lower detection limit and may also be measured with errors. The results based on linear and non‐linear covariate models are compared and new insights are gained.
Populational brain models of diffusion tensor imaging for statistical analysis: a complementary information in common space

Abstract Introduction : The search for human brain templates has been progressing in the past decades and in order to understand disease patterns a need for a standard diffusion tensor imaging (DTI) dataset was raised. For this purposes, some DTI templates were developed which assist group analysis studies. In this study, complementary information to the most commonly used DTI template is proposed in order to offer a patient-specific statistical analysis on diffusion-weighted data. Methods : 131 normal subjects were used to reconstruct a population-averaged template. After image pre processing, reconstruction and diagonalization, the eigenvalues and eigenvectors were used to reconstruct the quantitative DTI maps, namely fractional anisotropy (FA), mean diffusivity (MD), relative anisotropy (RA), and radial diffusivity (RD). The mean absolute error (MAE) was calculated using a voxel-wise procedure, which informs the global error regarding the mean intensity value for each quantitative map.
Understanding the Mechanisms for Tropical Surface Impacts of the Quasi‐Biennial Oscillation (QBO)

The impact of the quasi‐biennial oscillation (QBO) on tropical convection and precipitation is investigated through nudging experiments using the UK Met Office Hadley Center Unified Model. The model control simulations show robust links between the internally generated QBO and tropical precipitation and circulation. The model zonal wind in the tropical stratosphere was nudged above 90 hPa in atmosphere‐only and coupled ocean‐atmosphere configurations. The convection and precipitation in the atmosphere‐only simulations do not differ between the experiments with and without nudging, which may indicate that SST‐convection coupling is needed for any QBO influence on the tropical lower troposphere and surface. In the coupled experiments, the precipitation and sea‐surface temperature relationships with the QBO phase disappear when nudging is applied. Imposing a realistic QBO‐driven static stability anomaly in the upper‐troposphere lower‐stratosphere is not sufficient to simulate tropical surface impacts. The nudging reduced the influence of the lower troposphere on the upper branch of the Walker circulation, irrespective of the QBO, indicating that the upper tropospheric zonal circulation has been decoupled from the surface by the nudging. These results suggest that grid‐point nudging mutes relevant feedback processes occurring at the tropopause level, including high cloud radiative effects and wave mean flow interactions, which may play a key role in stratospheric‐tropospheric coupling.
Plasma cells are not restricted to the CD27+ phenotype: characterization of CD27-CD43+ antibody-secreting cells

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders. Conclusion we characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.