Miracle-dz/UniFAR-FTUs huggingface dataset:
Bias in mixtures of normal distributions and joint modeling of longitudinal and time-to-event data with monotonic change curves

Estimating parameters in a mixture of normal distributions dates back to the 19th century when Pearson originally considered data of crabs from the Bay of Naples. Since then, many real world applications of mixtures have led to various proposed methods for studying similar problems. Among them, maximum likelihood estimation (MLE) and the continuous empirical characteristic function (CECF) methods have drawn the most attention. However, the performance of these competing estimation methods has not been thoroughly studied in the literature and conclusions have not been consistent in published research. In this article, we review this classical problem with a focus on estimation bias. An extensive simulation study is conducted to compare the estimation bias between the MLE and CECF methods over a wide range of disparity values. We use the overlapping coefficient (OVL) to measure the amount of disparity, and provide a practical guideline for estimation quality in mixtures of normal distributions. Application to an ongoing multi-site Huntington disease study is illustrated for ascertaining cognitive biomarkers of disease progression. We also study joint modeling of longitudinal and time-to-event data and discuss pattern-mixture and selection models, but focus on shared parameter models, which utilize unobserved random effects in order to “join” a marginal longitudinal data model and marginal survival model in order to assess an internal time-dependent covariate’s effect on time-to-event. The marginal models used in the analysis are the Cox Proportional Hazards model and the Linear Mixed model, and both of these models are covered in some detail before defining joint models and describing the estimation process. Joint modeling provides a modeling framework that accounts for correlation between the longitudinal data and the
Automatic generation and refinement of hypertext links

Abstract Current generation of hypertext systems suffer from the limitations that they are static in nature, and they do not support the automated process of link creation very well. Because of the efforts involved in manually creating links, the hyperbases created using these systems are seldom modified even when they were found not to fully support the requirements of the intended users. This paper studies the development of automated tools to aid in the process of link creation, browsing, and link refinement. Only relation links are considered in this study. The automated tools are developed to help in three of the major stages of developing and using hypertext applications: (a) during authoring to generate a set of relation links between pairs of nodes; (b) during browsing to recommend an optimal set of starting nodes for the users to begin browsing, and to guide the users at each stage of browsing by suggesting a set of “next” nodes to traverse; and, (c) during training to modify, remove and add link.
Comparison of MOSFET mismatch models with random physical and random model variables

A comparison between two established MOSFET mismatch modeling approaches, one based upon the use of uncorrelated random physical variables and one based upon the use of correlated random model variables where the correlation is ignored, is presented. An analytical formulation is introduced that enables the designer to easily predict the relative errors in matching performance that will occur if the more popular random model parameters are used instead of the uncorrelated physical parameters. It is shown that neglecting the correlation inherent in the random model variables will result in under-estimate of the area required for meeting a fixed yield target but in the example process considered in this paper, the errors introduced by using the correlated model parameters are small.
Hardware-efficient implementation of WFQ algorithm on NetFPGA-based OpenFlow switch

The development of network services makes their requirements for bandwidth become higher and more various, which leads to difficulty in Quality of Service (QoS) guarantee. In this paper, an OpenFlow switch featuring Weighted Fair Queuing (WFQ) algorithm is proposed. The system is implemented into NetFPGA 1G board which utilizes Xilinx Virtex II Pro 50 technology. The results have shown that our circuit can deliver adequate level of QoS at a throughput of 8 Gbps in its current implementation. Due to the flexibility of the design, the WFQ circuit can be targeted for later technologies in order to provide higher throughput.
An AP2/ERF transcription factor ERF139 coordinates xylem cell expansion and secondary cell wall deposition.

Differentiation of xylem elements involves cell expansion, secondary cell wall deposition and programmed cell death. Transitions between these phases require strict spatiotemporal control. The function of Populus ERF139 (Potri.013G101100) in xylem differentiation was characterized in transgenic overexpression and dominant repressor lines of ERF139 in hybrid aspen (Populus tremula x tremuloides). Xylem properties, secondary cell wall (SCW) chemistry and downstream targets were analyzed in both types of transgenic trees using microscopy techniques, FT-IR, pyrolysis-GC/MS, wet chemistry methods and RNA sequencing. Opposite phenotypes were observed in the secondary xylem vessel sizes and SCW chemistry in the two different types of transgenic trees, supporting the function of ERF139 in suppressing the radial expansion of vessel elements and stimulating accumulation of guaiacyl-type lignin and possibly also xylan. Comparative transcriptomics identified genes related to SCW biosynthesis (LAC5, LBD15, MYB86) and salt and drought stress responsive genes (ANAC002, ABA1) as potential direct targets of ERF139. The phenotypes of the transgenic trees and the stem expression profiles of ERF139 potential target genes support the role of ERF139 as a transcriptional regulator of xylem cell expansion and SCW formation, possibly in response to osmotic changes of the cells. This article is protected by copyright. All rights reserved.
Task-independent robotic uncalibrated hand-eye coordination based on the extended state observer

This paper proposes a standard method to approach the uncalibrated robotic hand-eye coordination problem that is system configuration- and task-independent. The unknown hand-eye relationship is first modeled as the modeling errors of a dynamic system. An extended state observer is then implemented to estimate summation of the system's modeling error and the system's external disturbances. With the estimation results as the compensation, the system control is accomplished from a nonlinear combination of the system state errors. A universal framework of controller design is provided for decoupled and coupled hand-eye systems of different configurations to execute dynamic tracking task.
Environmental Toxicology and Chemistry

An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway‐ based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual‐based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Canine-Assisted Interviews Bolster Informativeness for Negative Autobiographical Memories

Humans and animals share a unique bond. Professionals are capitalizing on the human–animal bond by incorporating animals into therapy, forensic interviews, and the courtroom. However, the mnemonic consequence for including dogs in forensic interviews has not been empirically evaluated. In the current study, we examined whether the use of dogs increases the quantity of verbal reports for emotional events. Undergraduate participants were randomly assigned to dog or no dog conditions. Participants were interviewed about positive experienced events and negative experienced events. All interviews were audio recorded, transcribed verbatim, and analyzed for quantity of new information. Participants shared more new information in negative event reports with a dog present than with no dog present. There were no significant differences in the quantity of information disclosed for positive event memories between dog conditions. Canine-assisted interviews may provide comfort to people, resulting in more elaborative autobiographical reports about negative stressful events.
Molecular Basis of Tobacco-Induced Bacterial Biofilms

Objective To evaluate changes in the expression of biofilm-related genes when exposed to tobacco smoke and oxidative stress. Study Design Experimental, in vitro. Setting Laboratories of Rhinology and Microbiology, University of Pennsylvania. Subjects and Methods Bacterial biofilm mass was measured using crystal violet staining and measurement of the optical density. Biofilm-related genes of the Pseudomonas aeruginosa PAO1 strain (pilF, flgK, lasI, lasB, rhlA, and algC) were studied following repetitive exposure to exogenous tobacco smoke and hydrogen peroxide. This was done using a reporter plasmid. Results After 1 exposure to smoke, there was no change in biofilm formation. However, after 2 and 3 exposures, the biofilm formed had an increased mass (P < .05). With respect to oxidative stress in the form of H2O2, bacterial cultures demonstrated a dose- and time-dependent induction of biofilm formation compared with control conditions. Gene expression following repetitive smoke exposure demonstrated an increase in expression of pilF, flgK, algC, and lasI genes (P < .05); a decrease in rhlA (P < .05); and no significant change in the lasB gene (P = 0.1). Gene expression following H2O2 exposure demonstrated an increase in pilF (P < .05), whereas the other genes failed to demonstrate a statistical change. Conclusions Repetitive tobacco smoke exposure leads to molecular changes in biofilm-related genes, and exposure to oxidative stress in the form of H2O2 induces biofilm growth in PAO1. This could represent adaptative changes due to oxidative stress or chemically mediated through any of the several chemicals encountered in tobacco smoke and may explain increased biofilm formation in microbes isolated from smokers.
The Farnesoid X Receptor Controls Gene Expression in a Ligand- and Promoter-selective Fashion*

Farnesoid X receptor (FXR) is a nuclear receptor for bile acids. Ligand activated-FXR regulates transcription of genes to allow feedback control of bile acid synthesis and secretion. There are five major bile acids in humans. We have previously demonstrated that lithocholate acts as an FXR antagonist, and here we show that the other four bile acids, chenodeoxycholate (CDCA), deoxycholate (DCA), cholate (CA), and ursodeoxycholate (UDCA), act as selective FXR agonists in a gene-specific fashion. In an in vitro coactivator association assay, CDCA fully activated FXR, whereas CA partially activated FXR and DCA and UDCA had negligible activities. Similar results were also obtained from a glutathione S-transferase pull-down assay in which only CDCA and the synthetic FXR agonist GW4064 significantly increased the interaction of SRC-1 with FXR. In FXR transactivation assays with a bile salt export pump (BSEP) promoter-driven luciferase construct, bile acids showed distinct abilities to activate the BSEP promoter: CDCA, DCA, CA, and UDCA increased luciferase activity by 25-, 20-, 18-, and 8-fold, respectively. Consistently, CDCA increased BSEP mRNA by 750-fold in HepG2 cells, whereas DCA, CA, and UDCA induced BSEP mRNA by 250-, 75-, and 15-fold, respectively. Despite the partial induction of BSEP mRNA, CA, DCA, and UDCA effectively repressed expression of cholesterol 7α-hydroxylase, another FXR target. We further showed that all four bile acids significantly increased FXR protein, suggesting the existence of an auto-regulatory loop in FXR signaling pathways. In conclusion, these results suggest that the binding of each bile acid results in a different FXR conformations, which in turn differentially regulates expression of individual FXR targets.
Cell Membrane‐Camouflaged NIR II Fluorescent Ag2Te Quantum Dots‐Based Nanobioprobes for Enhanced In Vivo Homotypic Tumor Imaging

The advantages of fluorescence bioimaging in the second near‐infrared (NIR II, 1000–1700 nm) window are well known; however, current NIR II fluorescent probes for in vivo tumor imaging still have many shortcomings, such as low fluorescence efficiency, unstable performance under in vivo environments, and inefficient enrichment at tumor sites. In this study, Ag2Te quantum dots (QDs) that emit light at a wavelength of 1300 nm are assembled with poly(lactic‐co‐glycolic acid) and further encapsulated within cancer cell membranes to overcome the shortcomings mentioned above. The as‐prepared ≈100 nm biomimetic nanobioprobes exhibit ultrabright (≈60 times greater than that of free Ag2Te QDs) and highly stable (≈97% maintenance after laser radiation for 1 h) fluorescence in the NIR II window. By combining the active homotypic tumor targeting capability derived from the source cell membrane with the passive enhanced permeation and retention effect, improved accumulation at tumor sites ((31 ± 2)% injection dose per gram of tumor) and a high tumor‐to‐normal tissue ratio (13.3 ± 0.7) are achieved. In summary, a new biomimetic NIR II fluorescent nanobioprobe with ultrabright and stable fluorescence, homotypic targeting and good biocompatibility for enhanced in vivo tumor imaging is developed in this study.
Correction: Perceptual decisions are biased by the cost to act

Copyright Hagura et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Abstract Perceptual decisions are classically thought to depend mainly on the stimulus characteristics, probability and associated reward. However, in many cases, the motor response is considered to be a neutral output channel that only reflects the upstream decision. Contrary to this view, we show that perceptual decisions can be recursively influenced by the physical resistance applied to the response. When participants reported the direction of the visual motion by left or right manual reaching movement with different resistances, their reports were biased towards the direction associated with less effortful option. Repeated exposure to such resistance on hand during perceptual judgements also biased subsequent judgements using voice, indicating that effector-dependent motor costs not only biases the report at the stage of motor response, but also changed how the sensory inputs are transformed into decisions. This demonstrates that the cost to act can influence our decisions beyond the context of the specific action.
Chlorhexidine skin symptoms and allergy in dialysis patients and nurses

Chlorhexidine is a synthetic biguanide used as an antiseptic in hospital and household products. Chlorhexidine exposure has been implicated in various hypersensitivity reactions, including allergic contact dermatitis, fixed drug eruptions, occupational asthma, generalized urticaria, and anaphylaxis. Perioperative anaphylactic reactions to chlorhexidine have been reported since the 1990s and are typically caused by chlorhexidine-containing lubricants for in-dwelling urinary catheters, chlorhexidine-coated central venous catheters (CVCs), and topical chlorhexidine application. Up to 9% of cases of IgE-mediated perioperative anaphylaxis in the U.K. have been attributable to chlorhexidine; a similar figure has been reported in by a Danish study. This article is protected by copyright. All rights reserved.
Analysis of hard tissue regeneration and Wnt signalling in dental pulp tissues after direct pulp capping with different materials.

AIM To investigate the involvement of Wnt signalling and cell cycle regulation in hard tissue formation after pulp capping with several materials in a rat molar pinpoint exposure model. METHODOLOGY Thirty-two rat molar pulps were mechanically exposed and assigned to 4 groups according to the pulp capping materials used Ca(OH)2 , mineral trioxide aggregate (MTA), Biodentine™ and an untreated control group. After 4 weeks, the teeth were collected for microcomputed tomography to quantify reparative dentine formation. Histological analysis was then performed to evaluate the quality of the reparative dentine and the dental pulp tissue inflammatory reaction. Cyclin D1 and β-catenin expression was examined using immunofluorescence staining. The Kruskal-Wallis followed by Dunn's multiple comparison test was performed to determine significant differences. RESULTS The exposed dental pulps treated with Ca(OH)2 , MTA and Biodentine™ exhibited reparative dentine formation near the exposure site. Fibrous tissues adjacent to the exposure site were observed in the untreated group. The microcomputed tomography evaluation of MTA and Biodentine™ groups revealed significantly greater reparative dentine formation compared with the control group (P = 0.0032 in the MTA group and P = 0.05 in the BiodentineTM group). From histological evaluations, the BiodentineTM group exhibited significantly greater reparative dentine formation grading compared with the control group (P = 0.0152). The pulp tissues treated with Ca(OH)2 and Biodentine™ exhibited a lower inflammatory score compared with those of the untreated control (P = 0.0291 in the Ca(OH)2 and P = 0.0110 in the BiodentineTM group). Ca(OH)2 , MTA and Biodentine™ induced cyclin D1 expression in the dental pulp tissues adjacent to the reparative dentine. Moreover, the Biodentine™-treated defects demonstrated β-catenin expression in the pulp tissue adjacent to the newly formed reparative dentine, which was not observed with the other materials. CONCLUSION All test materials promoted dentine bridge formation and stimulated cyclin D1 expression. The favourable outcome after direct pulp capping with Biodentine™ involved Wnt/β-catenin signalling. However, Wnt/β-catenin signalling did not participate in the mechanism by which Ca(OH)2 and MTA promoted reparative dentine formation.
Role for diet in normal gut barrier function: developing guidance within the framework of food-labeling regulations

A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharide, peptidoglycan, whole bacteria, and other toxins to traverse the barrier to damage the intestine or enter the portal circulation. Currently available evidence in animal models and in vitro systems has shown that certain dietary interventions can be used to reinforce the intestinal barrier to prevent the development of disease. The relevance of these studies to human health is unknown. Herein, we define the components of the intestinal barrier, review available modalities to assess its structure and function in humans, and review the available evidence in model systems or perturbations in humans that diet can be used to fortify intestinal barrier function. Acknowledging the technical challenges and the present gaps in knowledge, we provide a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease. Such evidence would provide information on the development of healthier diets and serve to provide a framework by which federal agencies such as the US Food and Drug Administration can evaluate evidence linking diet with normal human structure/function claims focused on reducing risk of disease in the general public.
Study on the Growth and Enterotoxin Production by Staphylococcus aureus in Canned Meat before Retorting

Possible contamination by Staphylococcus aureus of the production environment and of the meat of a canned meat production factory was analysed. A total of 108 samples were taken from nine critical control points, 13 of them were positive for S. aureus. None of the isolates produced enterotoxins. To determine how much time can elapse between can seaming and sterilisation in the autoclave without any risk of enterotoxin production by S. aureus, the growth and enterotoxin production of three enterotoxin A producing strains of S. aureus (one ATCC strain and two field strains) in canned meat before sterilisation was investigated at three different temperatures (37, 20 and 10 °C). Two types of meat were used, one with and one without sodium nitrite. In the canned products, the spiked bacteria spread throughout the meat and reached high levels. Enterotoxin production was shown to start 10 hours after incubation at 37 °C and after 48 h after incubation at 20 °C; the production of enterotoxin was always detected in the transition between the exponential and the stationary growth phase. At 10 °C, the enterotoxin was never detected. The statistical analysis of the data showed that the difference between the two different types of meat was not statistically significant (p value > 0.05). Since it is well known that following heat treatment, staphylococcal enterotoxins, although still active (in in vivo assays), can be undetectable (loss of serological recognition) depending on the food matrix and pH, it is quite difficult to foresee the impact of heat treatment on enterotoxin activity. Therefore, although the bacteria are eliminated, the toxins may remain and cause food poisoning. The significance of the results of this study towards implementing good manufacturing practices and hazard analysis critical control points in a canned meat factory are discussed with reference to the management of pre-retorting steps after seaming.