Miracle-dz/UniFAR-FTUs huggingface dataset:
Tempering the wrath of RAGE: An emerging therapeutic strategy against diabetic complications, neurodegeneration, and inflammation

The multiligand receptor RAGE (receptor for advanced glycation end-products) is emerging as a central mediator in the immune/inflammatory response. Epidemiological evidence accruing in the human suggests upregulation of RAGE's ligands (AGEs, S100/calgranulins, high mobility group box-1 (HMGB1), and amyloid β-peptide and β-sheet fibrils) and the receptor itself at sites of inflammation and in chronic diseases such as diabetes and neurodegeneration. The consequences of ligand-RAGE interaction include upregulation of molecules implicated in inflammatory responses and tissue damage, such as cytokines, adhesion molecules, and matrix metalloproteinases. In this review, we discuss the localization of RAGE and its ligand families and the biological impact of this axis in multiple cell types implicated in chronic diseases. Lastly, we consider findings from animal model studies suggesting that although tissue-damaging effects ensue from recruitment of the ligand-RAGE interaction, in distinct settings, adaptive and repair/regeneration outcomes appear to override detrimental effects of RAGE. As RAGE blockade moves further into clinical development, clarifying the biology of RAGE garners ever-increasing importance.
Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S]

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism.
Manual vs. Automated Vulnerability Assessment: A Case Study

The dream of every software development team is to assess the security of their software using only a tool. In this paper, we attempt to evaluate and quantify the effectiveness of automated source code analysis tools by comparing such tools to the results of an in-depth manual evaluation of the same system. We present our manual vulnerability assessment methodology, and the results of applying this to a major piece of software. We then analyze the same software using two commercial products, Coverity Prevent and Fortify SCA, that perform static source code analysis. These tools found only a few of the fifteen serious vulnerabilities discovered in the manual assessment, with none of the problems found by these tools requiring a deep understanding of the code. Each tool reported thousands of defects that required human inspection, with only a small number being security related. And, of this small number of security-related defects, there did not appear to be any that indicated significant vulnerabilities beyond those found by the manual assessment.
Equivalence Relations of Resonant Tanks: A New Perspective for Selection and Design of Resonant Converters

There are various resonant tanks for constructing resonant converters. In this paper, the equivalence relations of resonant tanks are investigated, which bring a new perspective for analysis of resonant converters. On one hand, the equivalence relations can help select suitable resonant converter topologies for specific applications, which is illustrated by the examples of the LLC resonant converter and CLL resonant converter, and LCC resonant converter and hybrid series-parallel resonant converter (HSPRC). On the other hand, the equivalence relations can help to simplify the design of some high-order resonant converters, which is illustrated by the example of the LLC resonant converter and LLC-L resonant converter.
Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance

The nuclear pore complex (NPC) mediates all nucleocytoplasmic transport, yet its structure and biogenesis remain poorly understood. In this study, we have functionally characterized interaction partners of the yeast transmembrane nucleoporin Ndc1. Ndc1 forms a distinct complex with the transmembrane proteins Pom152 and Pom34 and two alternative complexes with the soluble nucleoporins Nup53 and Nup59, which in turn bind to Nup170 and Nup157. The transmembrane and soluble Ndc1-binding partners have redundant functions at the NPC, and disruption of both groups of interactions causes defects in Ndc1 targeting and in NPC structure accompanied by significant pore dilation. Using photoconvertible fluorescent protein fusions, we further show that the depletion of Pom34 in cells that lack NUP53 and NUP59 blocks new NPC assembly and leads to the reversible accumulation of newly made nucleoporins in cytoplasmic foci. Therefore, Ndc1 together with its interaction partners are collectively essential for the biosynthesis and structural integrity of yeast NPCs.
Plasma and Tissue Determination of 4-Methylpyrazole for Pharmacokinetic Analysis in Acute Adult and Pediatric Methanol/Ethylene Glycol Poisoning

Methanol and ethylene glycol poisoning may result in severe intoxication. The inhibition of alcohol dehydrogenase by ethanol or 4-methylpyrazole (4-MP, fomepizole) is fundamental to their treatment. 4-MP presents several advantages over ethanol therapy and has been recently approved as a specific antidote for both intoxications. The authors have developed a simple gas chromatographic method to determine blood and tissue 4-MP concentrations. This method has been validated for its reproducibility (between-day CV < 6.3%), sensitivity (LOD 0.2 μg/mL), and linearity. It has been used in 4 adult patients intoxicated by methanol and 1 child accidentally intoxicated by ethylene glycol. 4-MP was used for each patient, and its blood levels were monitored every 4 hours over 2–3 days for pharmacokinetics purposes. In the population studied, after repeated administration of 10 mg/kg fomepizole, plasma 4-MP concentrations ranged from 1.4 to 21.6 μg/mL, always above the active level of 0.8 μg/mL. The mean peak concentration observed in the 4 adult patients was 18.5 ± 2.6 μg/mL and in the child was 18.9 ± 2.2 μg/mL. Even though 4-MP is characterized by a dose-dependent kinetic profile, under our conditions of dosage and blood sampling, its elimination better fitted a first-order kinetic model. At steady state and without any concomitant therapies, the mean apparent elimination half-life was 14.5 ± 3 hours. Elimination seemed faster in the child. A trend toward a progessive enhancement of the 4-MP elimination rate is suggested in the pediatric case, with the duration of the treatment resulting in a t½ below 5 hours after 48 hours. One patient died, and samples of blood and hepatic tissue were removed simultaneously during autopsy for 4-MP analysis. Interestingly, when the plasma concentration was subtherapeutic (<1 μg/mL) the tissue concentration observed was still significant with 12 μg/g, supporting an intermittent scheme of administration.
An Autonomous Road Side Infrastructure Based System in Secure VANETs

Road side infrastructures with certification and service aid are important in secure vehicular communication. Few road side infrastructure issues have been addressed in former studies. Lacking trusted certification, scalability, efficiency and intrusion detection in vehicle-only network causes various attacks. In this paper we propose an autonomous road side infrastructure network approach. Some road side infrastructures are preselected administratively and the others gather towards the formers autonomously. Road side infrastructures in the same autonomous network cache and forward certificates, which are invisible to other autonomous network. In our approach, CA cluster in different regions comply with corresponding scalability strategy and regional policy. A distributed IDS system integrated with the CA database provide further security protection from malicious vehicles with legal certificates. The certificate caching and forwarding schema accelerates authentication. In our analysis, our approach has a better efficiency, scalability and security guarantee than former road side infrastructure designs.
IL-33 and Airway Inflammation

Interleukin-33 (IL-33) is the 11th member of IL-1 cytokine family which includes IL-1 and IL-18. Unlike IL-1β and IL-18, IL-33 is suggested to function as an alarmin that is released upon endothelial or epithelial cell damage and may not enhance acquired immune responses through activation of inflammasome. ST2, a IL-33 receptor component, is preferentially expressed by T-helper type (Th) 2 cells, mast cells, eosinophils and basophils, compared to Th1 cells, Th17 cells and neutrophils. Thus, IL-33 profoundly enhances allergic inflammation through increased expression of proallergic cytokines and chemokines. Indeed, IL-33 and its receptor genes are recognized as the most susceptible genes for asthma by several recent genomewide association studies. It has also recently been shown that IL-33 plays a crucial role in innate eosinophilic airway inflammation rather than acquired immune responses such as IgE production. As such, IL-33 provides a unique therapeutic way for asthma, i.e., ameliorating innate airway inflammation.
Components of the fibrinolytic system Plasminogen

The molecular mechanisms that finely co-ordinate fibrin formation and fibrinolysis are now well defined. The structure and function of all major fibrinolytic proteins, which include serine proteases, their inhibitors, activators and receptors, have been characterized. Measurements of real time, dynamic molecular interactions during fibrinolysis of whole blood clots can now be carried out in vitro. The development of genetargeted mice deficient in one or more fibrinolytic protein(s) has demonstrated expected and unexpected roles for these proteins in both intravascular and extravascular settings. In addition, genetic analysis of human deficiency syndromes has revealed specific mutations that result in human disorders that are reflective of either fibrinolytic deficiency or excess. Elucidation of the fine control of fibrinolysis under different physiological and pathological haemostatic states will undoubtedly lead to novel therapeutic interventions. Here, we review the fundamental features of intravascular plasmin generation, and consider the major clinical syndromes resulting from abnormalities in fibrinolysis.
Perceived religious support for problem gambling: does church doctrine influence help-seeking?

This project explored church members’ willingness to use religious resources to overcome a gambling problem. Participants from congregations with divergent doctrine on gambling (Roman Catholic, n = 156; Southern Baptist, n = 93) were randomly assigned to imagine having gambling or depression problems. Expected religious support and the likelihood of asking for help were evaluated using analysis of variance. Church doctrine on gambling did not relate with anticipated social support or likelihood of seeking help. Most participants expected support from church, and were willing to seek help from church members. Southern Baptists, compared to Catholics, did expect more forgiveness. Participants in the gambling condition, compared to the depression condition, expected more judgement. Individuals in the gambling condition, compared to the depression condition, were more likely to seek help from church resources. These findings suggest that religious individuals view gambling as a moral problem, and that the church will be seen as a treatment resource.
‘How does TGfU work?’: examining the relationship between learning design in TGfU and a nonlinear pedagogy

Background: In the last few decades, conceptions about teaching and learning in physical education have evolved from a teacher-centred approach to a more student-centred approach where learners are encouraged to develop problem-solving skills, critical thinking and autonomy of thought. A popular model advocating this approach in physical education, Teaching Games for Understanding (TGfU), has attracted widespread attention. Although advocates of TGfU have provided some empirical and anecdotal evidence to support the ‘tactical over technical approach’ to games teaching, recent work has highlighted that to date, the question ‘Does TGfU work? ’ has remained largely unanswered. Therefore, there is a need to research the intuitive assumptions about how students learn to play games and to understand how the TGfU approach might work for games teaching and learning. Purpose: The purpose of this paper is to provide insights to further our understanding of the possible processes underpinning the pedagogical principles of TGfU in games teaching. In this regard, we outline how a Nonlinear Pedagogy approach could provide a theoretical rationale to explain how the principles of TGfU might support learning design for games teaching. To achieve this aim, we examined the viability of the four key pedagogical principles of the TGfU model and highlighted the theoretical and practical implications of Nonlinear Pedagogy, considered with some empirical evidence from the motor learning literature. Findings: The theoretical ideas emanating from an ecological dynamics perspective, such as constraints manipulation, importance of maintaining information-movement coupling and harnessing movement variability, can underpin a Nonlinear Pedagogy approach. It has been proposed that research evidence from the motor learning literature can provide a suitable theoretical grounding to support the viability of the four main pedagogical principles of the TGfU model (i.e., sampling, tactical complexity, representation and exaggeration) and can contribute insights to the possible processes of TGfU in games teaching. Summary: A Nonlinear Pedagogy approach has the potential to provide researchers and physical educators with an understanding of the theoretical and practical work on TGfU, in association with its pedagogical principles. Understanding the underlying processes linked to the key pedagogical principles in learning design is critical for addressing pedagogy and curriculum concerns in physical education to enhance student learning. The ideas raised in this paper provided some rationale for the efficacy of the model, and also a platform for researchers and practitioners to more effectively engage students using the TGfU model.
Visual assessment techniques for component-based framework evolution

Many component models have been proposed to address the challenge of reducing software development time and costs. Such models often offer similar functionality. We study how developers can assess the relative strengths and weaknesses of such models, based on information about the component development process, and the component framework performance. We use a visual tool to gather such information and support our approach. We validate our approach on ROBOCOP, a complex component framework used in the industry.
Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas.

BACKGROUND Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-like markers (CD133, paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. METHODS In 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins. RESULTS CD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis. PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed. CONCLUSION Detecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.
Psychological Outcomes of Patients With Screen-Detected Type 2 Diabetes

OBJECTIVE—The objective of this study was to investigate how time since diagnosis and treatment intensity influence psychological outcomes in patients with screen-detected type 2 diabetes. RESEARCH DESIGN AND METHODS—A 2 × 2 factorial cross-sectional design was used to examine psychological outcomes in 196 patients with screen-detected diabetes diagnosed 3–33 months previously who were receiving usual care or intensive multifactorial pharmacological treatment. Outcomes included anxiety, depression, diabetes-related distress, perceived seriousness and vulnerability, self-efficacy, and self-care. Multivariate analysis was used to examine variations in outcomes based on time since diagnosis (<1 vs. 2–3 years) and treatment intensity. RESULTS—Most patients reported little distress, low perceived seriousness and vulnerability, high self-efficacy, and low self-care, but outcomes varied considerably across conditions. Time effects were found for perceived vulnerability, which increases significantly with time since diagnosis. Time × treatment interactions were found for anxiety, diabetes-related distress, and self-efficacy; notably, intensively treated patients showed more distress and less self-efficacy in the 1st year, and usual-care patients reported more distress and less self-efficacy 2–3 years after diagnosis. CONCLUSIONS—Screen-detected patients generally do not experience much difficulty with their condition in the first few years, but early and intensive treatment can influence patients’ psychological outcomes, leading to relatively more anxiety and less self-efficacy in the 1st year after diagnosis but not necessarily improving self-care. This suggests that intensive treatments confront patients with their diabetes earlier on whereas milder treatments may delay confrontation. This finding should be taken into account in the development and timing of psychological interventions for patients with newly diagnosed diabetes.
The collaboration of both humoral and cellular HER-2/neu-targeted immune responses is required for the complete eradication of HER-2/neu-expressing tumors.

HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients with neu-expressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination in neu-N mice. In contrast, a significant induction of both neu-specific T-cell and antibody responses is found in nontoleragenic FVB/N mice after vaccination. These mice are fully protected from a s.c. challenge with NT cells, a mammary tumor cell line derived from a spontaneous tumor that arose in a neu-N mouse, whereas neu-N mice are not. In this study, we demonstrate that CD4+ T cell-depleted FVB/N mice show no induction of neu-specific IgG after vaccination and are unable to reject an NT challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were tumor free). In CD8+ T cell-depleted animals, where vaccine-induced neu-specific IgG titers were normal, NT growth was delayed, but only 10% of mice remained tumor free, demonstrating that neu-specific IgG alone is insufficient for protection from NT challenge. To directly assess the necessity for the combination of neu-specific cellular and humoral immune responses, severe combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG derived from FVB/N mice. Animals that were given CTLs that recognized an irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to CD8+ T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu-specific CTLs plus control IgG derived from naive FVB/N mice were only partially protected from NT challenge (50% of animals were tumor free). However, only animals receiving the combination of neu-specific CTLs and neu-specific IgG were fully protected from NT challenge (100% of animals were tumor free). These studies specifically define the immunological requirements for the eradication of neu-expressing tumors in this model system, demonstrating that both cellular and humoral neu-specific responses are necessary for protection from an NT challenge. These data suggest that vaccines optimized to induce maximal T- and B-cell immunity to neu, and possibly to similar putative tumor-rejection antigens, may lead to more potent in vivo antitumor immunity.
Hypersharpening by Joint-Criterion Nonnegative Matrix Factorization

Hypersharpening aims at combining an observable low-spatial resolution hyperspectral image with a high-spatial resolution remote sensing image, in particular a multispectral one, to generate an unobservable image with the high spectral resolution of the former and the high spatial resolution of the latter. In this paper, two such new fusion methods are proposed. These methods, related to linear spectral unmixing techniques, and based on nonnegative matrix factorization (NMF), optimize a new joint criterion and extend the recently proposed joint NMF (JNMF) method. The first approach, called gradient-based joint-criterion NMF (Grd-JCNMF), is a gradient-based method. The second one, called multiplicative JCNMF (Mult-JCNMF), uses new designed multiplicative update rules. These two JCNMF approaches are applied to synthetic and semireal data, and their effectiveness, in spatial and spectral domains, is evaluated with commonly used performance criteria. Experimental results show that the proposed JCNMF methods yield sharpened hyperspectral data with good spectral and spatial fidelities. The obtained results are compared with the performance of two NMF-based methods and one approach based on a sparse representation. These results show that the proposed methods significantly outperform the well-known coupled NMF sharpening method for most performance figures. Also, the proposed Mult-JCNMF method provides the results that are similar to those obtained by JNMF, with a lower computational cost. Compared with the tested sparse-representation-based approach, the proposed methods give better results. Moreover, the proposed Grd-JCNMF method considerably surpasses all other tested methods.