Miracle-dz/UniFAR-FTUs huggingface dataset:
cAMP-induced AQP2 translocation is associated with RhoA inhibition through RhoA phosphorylation and interaction with RhoGDI

We have recently demonstrated that inhibition of Rho GTPase with Clostridium difficile toxin B, or with Clostridium botulinum C3 toxin, causes actin depolymerization and translocation of aquaporin 2 (AQP2) in renal CD8 cells in the absence of hormonal stimulation. Here we demonstrate that Rho inhibition is part of the signal transduction cascade activated by vasopressin leading to AQP2 insertion into the apical membrane. Quantitation of active RhoA (GTP-bound) by selective pull down experiments demonstrated that the amount of active RhoA decreased upon stimulation of CD8 cells with the cAMP-elevating agent forskolin. Consistent with this observation, forskolin treatment resulted in a decreased expression of membrane-associated (active) Rho, as assessed by cell fractionation followed by western blotting analysis. In addition, the abundance of the endogenous Rho GDP dissociation inhibitor (Rho-GDI) was found to have decreased in the membrane fraction after forskolin stimulation. Co-immunoprecipitation experiments revealed that, after forskolin stimulation, the amount of Rho-GDI complexed with RhoA increased, suggesting that Rho GTPase inhibition occurs through association of RhoA with Rho-GDI. Finally, forskolin stimulation was associated with an increase in Rho phosphorylation on a serine residue, a protein modification known to stabilize the inactive form of RhoA and to increase its interaction with Rho-GDI. Taken together, these data demonstrate that RhoA inhibition through Rho phosphorylation and interaction with Rho-GDI is a key event for cytoskeletal dynamics controlling cAMP-induced AQP2 translocation.
Rethinking EU Trade Procedures - The Beer Living Lab

The EU is currently reshaping its customs legislation and practices. Main pillars in the new vision are an intensive use of IT (Customs becomes e-Customs), partnerships between Customs administrations and businesses, and collaboration between national Customs administrations. These concepts should support coping with the dilemma of on the one hand increasing security, safety, financial and health requirements, and on the other hand the need to reduce administrative burden, to keep the EU a competitive economic zone. Two main concepts in coping with this challenge are Single Window and Authorized Economic Operators. The EU is investigating how to transform these abstract concepts into a tangible reality. The Beer Living Lab is an EU-funded pilotconcepts into a tangible reality. The Beer Living Lab is an EU-funded pilot research project that implements this EU vision in the beer industry. In this paper we provide results from the Beer Living Lab and we introduce the fourth step in e-control, a theoretical framework for procedure redesign. We discuss the application of econtrol in the Beer Living Lab, where modeling is a means to facilitate innovation and network transformation.
The Superior Turbinate as a Source of Functional Human Olfactory Receptor Neurons

Objectives The function of human olfactory receptor neurons (ORNs) remains incompletely understood, in part because of the difficulty of obtaining viable olfactory tissue for study. During endoscopic sphenoidotomy, a portion of the superior turbinate is often removed to achieve wide and safe access to the sphenoid sinus. The purpose of this study was to determine whether functional olfactory mucosa could be obtained from such superior turbinate tissue.
P2X7 Nucleotide and EGF Receptors Exert Dual Modulation of the Dual-Specificity Phosphatase 6 (MKP-3) in Granule Neurons and Astrocytes, Contributing to Negative Feedback on ERK Signaling

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play a central role in the intracellular signaling of P2X7 nucleotide receptors in neurons and glial cells. Fine spatio-temporal tuning of mitogen-activated protein (MAP) kinases is essential to regulate their biological activity. MAP kinase phosphatases (MKPs) are dual specificity protein phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues in MAP kinases. This study focuses on how DUSP, DUSP6/MKP3, a phosphatase specific for ERK1/2 is regulated by the P2X7 nucleotide receptor in cerebellar granule neurons and astrocytes. Stimulation with the specific P2X7 agonist, BzATP, or epidermal growth factor (EGF) (positive control for ERK activation) regulates the levels of DUSP6 in a time dependent manner. Both agonists promote a decline in DUSP6 protein, reaching minimal levels after 30 min yet recovering to basal levels after 1 h. The initial loss of protein occurs through proteasomal degradation, as confirmed in experiments with the proteasome inhibitor, MG-132. Studies carried out with Actinomycin D demonstrated that the enhanced transcription of the Dusp6 gene is responsible for recovering the DUSP6 protein levels. Interestingly, ERK1/2 proteins are involved in the biphasic regulation of the protein phosphatase, being required for both the degradation and the recovery phase. We show that direct Ser197 phosphorylation of DUSP6 by ERK1/2 proteins could be part of the mechanism regulating their cytosolic levels, at least in glial cells. Thus, the ERK1/2 activated by P2X7 receptors exerts positive feedback on these kinase’s own activity, promoting the degradation of one of their major inactivators in the cytosolic compartment, DUSP6, both in granule neurons and astrocytes. This feedback loop seems to function as a common universal mechanism to regulate ERK signaling in neural and non-neural cells.
DeepAD: Alzheimer’s Disease Classification via Deep Convolutional Neural Networks using MRI and fMRI

To extract patterns from neuroimaging data, various statistical methods and machine learning algorithms have been explored for the diagnosis of Alzheimer’s disease among older adults in both clinical and research applications; however, distinguishing between Alzheimer’s and healthy brain data has been challenging in older adults (age > 75) due to highly similar patterns of brain atrophy and image intensities. Recently, cutting-edge deep learning technologies have rapidly expanded into numerous fields, including medical image analysis. This paper outlines state-of-the-art deep learning-based pipelines employed to distinguish Alzheimer’s magnetic resonance imaging (MRI) and functional MRI (fMRI) from normal healthy control data for a given age group. Using these pipelines, which were executed on a GPU-based high-performance computing platform, the data were strictly and carefully preprocessed. Next, scale- and shift-invariant low- to high-level features were obtained from a high volume of training images using convolutional neural network (CNN) architecture. In this study, fMRI data were used for the first time in deep learning applications for the purposes of medical image analysis and Alzheimer’s disease prediction. These proposed and implemented pipelines, which demonstrate a significant improvement in classification output over other studies, resulted in high and reproducible accuracy rates of 99.9% and 98.84% for the fMRI and MRI pipelines, respectively. Additionally, for clinical purposes, subject-level classification was performed, resulting in an average accuracy rate of 94.32% and 97.88% for the fMRI and MRI pipelines, respectively. Finally, a decision making algorithm designed for the subject-level classification improved the rate to 97.77% for fMRI and 100% for MRI pipelines.
Un dictionnaire des collocations est-il possible?

Expose concernant les dictionnaires des collocations, depuis 1571 (Les epithetes de M. de La Porte, Parisien), jusqu'au dernier de 1931 (Les mots et les idees. Dictionnaire des termes cadrant avec les idees, par Ulysse Lacroix). Problematique d'un dictionnaire contemporain.
Average dwell-time conditions of switching information topologies for consensus of linear multi-agent systems

In this paper, we study the consensus problem of linear multi-agent systems (LMAS) in directed networks with switching information topology. The consensus problem is transformed into the partial stability problem of a corresponding auxiliary system by a linear transformation. For a pre-given set of topologies, We address two cases: 1) The LMAS achieves the consensus under each fixed information topology in this set; 2) The LMAS achieves the consensus under some information topologies in this set. For both cases, we present sufficient conditions that sustain the consensus of the LMAS with switching topology under an average dwell time scheme, respectively. Simulation results are also given to demonstrate the effectiveness of the theoretical results.
Self-reported Oral Hygiene Habits in Smokers and Nonsmokers Diagnosed with Periodontal Disease.

PURPOSE To determine whether smokers report having less adequate oral hygiene habits than nonsmokers. MATERIALS AND METHODS Using a 24-item questionnaire addressing both smoking and oral hygiene habits, patients from three periodontal practices in Spain were evaluated. In order to assess the periodontal status of all patients, immediately following the survey, the patients were examined clinically and categorised according to the American Dental Association (ADA) classification for periodontal diseases. RESULTS 762 patients with ADA type I gingivitis (4.1%), type II early periodontitis (31.2%), type III moderate periodontitis (39.2%) and type IV advanced periodontitis (25.5%) were surveyed. A total of 289 smokers (38.0%) and 402 (52.8%) nonsmokers participated in the study: 77 (10.1%) participants were identified as heavy smokers (>20 cigarettes/day), along with 122 (16.0%) moderate smokers (10-20 cigarettes/day) and 90 (11.8%) light smokers (<20 cigarettes/day). A greater proportion of nonsmokers brushed their teeth two (37.8%) or more (22.9%) times a day compared with moderate smokers (twice: 32.0%, more: 15.6%) and heavy smokers (twice: 32.5%, more: 15.6%), respectively (p < 0.05). Heavy smokers used dental floss statistically significantly less frequently (10.4%) than nonsmokers (21.6%) (p < 0.05). No statistically significant differences were found between smokers and nonsmokers regarding the use of mouthwashes (p > 0.05). CONCLUSIONS This study revealed comparable oral hygiene habits in nonsmokers and light smokers. However, heavy smokers were found to have worse oral hygiene habits than nonsmokers.
T h e M u l t i n a t i o n a l B u s i n e s s R e v i e w What is the Shape of the Multinationality-Performance Relationship?

Previous theoretical explanations and empirical analyses of the multinationality-performance relationship have produced mixed arguments and results. Linear and inverted U-shaped relationships have been theorized and confirmed empirically. Recent research has theorized that there is a three-stage, sigmoid relationship between multinationality and performance. We contribute to the debate by showing that the impact of multinationality depends on the time dimension incorporated in the performance measure; that is, the net benefits from multinationality are likely to be higher in the longer term. The results from our sample of US manufacturing multinationals indicate that there is a three-stage, sigmoid multinationality-performance relationship.
Duchenne Muscular Dystrophy: Therapeutic Approaches to Restore Dystrophin

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder. The first symptoms involve the lower limbs and appear between the third and fifth year. Due to weakness of the knee and hip extensors, patients rise from a sitting position using the Gower's maneuver. Muscle weakness progresses to the shoulder girdle-, upper arm and trunk-muscles and patients loose ambulation before the age of 12 (Emery, 1993). Histological changes involve variation in fiber size with atrophic and hypertrophic fibers, degeneration and regeneration of the muscle fibers, infiltration of inflammatory cells and fibrosis. The fiber necrosis results in leakage of the enzyme creatine kinase (CK), resulting in very high serum CK levels in DMD patients (20,000 to 50,000 U/L compared to 80 to 250 U/L in unaffected individuals). These levels decline as patients get older and the overall muscle mass decreases progressively. The pathology is caused by mutations in the DMD gene, which was known to be on the X chromosome long before the responsible gene was cloned due to an X-linked recessive inheritance pattern. The protein product of the gene is a 427 KDa protein called dystrophin. In the early 80s several groups were collaborating on the regional cloning of the gene responsible for DMD (Burghes et al., 1987; Monaco et al., 1985) which happened to co-localize with the locus for Becker muscular dystrophy (BMD) (Kingston et al., 1984). This is a milder disease, where patients are diagnosed in adolescence or adulthood, remain ambulant longer and survival is generally only slightly decreased (Emery, 2002). After a couple of years Monaco and colleagues confirmed that deletions in the identified locus caused DMD (Monaco et al., 1985) and BMD (Hoffman et al., 1988). In the following years, the coding sequence of the gene was identified, which turned out to occupy a huge genomic region. The complete cDNA and protein product of the DMD gene were published in 1987 (Hoffman et al., 1987; Koenig et al., 1987). The cloning of the genomic and coding sequence of the DMD gene allowed the development of tools for the molecular diagnosis of DMD. Deletions of one or more exons were found to be most common (65% of patients) and mainly localized in two hotspot regions in the gene (exons 220 and 45-53). This led Chamberlain and colleagues to develop a multiplex PCR able to detect the most frequent mutations (Chamberlain et al., 1988). This technique has been used for years, but recently multiple ligation-dependent probe amplification (MLPA) has been developed that allows an exact characterization of exons involved in deletions and duplications (Janssen et al., 2005; Schwartz & Duno, 2004). For small mutations a more
Distributed generation on distribution system voltage regulation: An optimization-based approach

We propose two optimization-based models for computing the allowable penetration level of multiple distributed generators, taking into account voltage regulation constraints. A single level optimization model is developed for computing the maximum penetration level, while a bi-level optimization model is developed to answer the question as to at least how much power a distribution system can accommodate. In the suggested models, on-load tap changing transformer is modeled in detail with a switch function, and the impact of distributed generator outages is included. Questions also answered in this study are how on-load tap changer can oscillate and what roles distributed generators play in this regard. Numerical algorithms are described, together with the simulation results of a 112 bus system.1
Visual performance: validation of the inventory of visual efficiency in students

Purpose: Translate and adapt the COVD-QoL questionnaire to Portuguese language and culture and assess the psychometric properties of the translated questionnaire. Methods: The questionnaire was adapted according to the methodology recommended by the literature. The final version of visual symptoms and quality of life questionnaire adapted to Portuguese (QSL-QOL) was applied in 130 volunteers, aged 18 to 30 years and 36 subjects completed the questionnaire at two different times. Results: The results showed good internal consistency for the full version with 30 items (α = 0.894) and for the short version with 19 items (0.858). The test re-test revealed an average of differences between the first and second evaluation of 0,917 points (SD = ± 4.813) which indicates a minimum bias between the two applications. Conclusions: The Portuguese version of COVD-QoL showed good psychometric properties and has been shown to be applicable to the Portuguese population, to evaluate visual discomfort associated with near vision in higher education students.
Five leading U.S. commercial brands of moist snuff in 1994: assessment of carcinogenic N-nitrosamines.

BACKGROUND Moist snuff is the only tobacco product in the United States with increasing sales (an increase of 38.4% between 1981 and 1993) and with increased consumption, primarily by male adolescents aged 12-18 years old and young adults aged 19 years old or older. It is known from previous studies that levels of nicotine and the proportion of unprotonated (free) nicotine, as well as the pH, which affects nicotine delivery, vary considerably among the leading snuff brands. Whether concentrations of major carcinogens, such as the nicotine-derived tobacco-specific N-nitrosamines (TSNAs), like N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), also vary among these brands has not been determined previously. PURPOSE Our purpose was threefold: 1) to determine the concentrations of major carcinogenic nicotine-derived N-nitrosamines in each of the five most popular moist snuff brands; 2) to analyze the quantitative differences in the various snuff components (e.g., NNN) between two major brand categories: a category comprising the brands known to have high levels of unprotonated nicotine (Copenhagen, Skoal fine cut, and Kodiak) versus a category comprising the brands known to have low levels (Hawken and Skoal Bandits); and 3) to compare the differences in the concentrations of nicotine (previously determined), NNN, NNK, and total TSNAs between these two major brand categories. METHODS Three boxes of each of the five leading U.S. moist snuff brands were bought in July 1994 from retailers in six areas and transferred immediately to the analytical laboratory. After extraction, N-nitrosamino acids and TSNAs were determined on a gas chromatograph interfaced with a thermal energy analyzer (GC-TEA) and integrator. Each 5-g sample of ground, freeze-dried tobacco was extracted twice, and each extract was analyzed twice by GC-TEA. All P values reported are two sided. RESULTS Copenhagen, Skoal fine cut, and Kodiak as a group had statistically significant higher levels of nicotine (P = .0017), NNN (P < .0001), NNK (P = .0119), and total TSNAs (P < .0001) than the Hawken and Skoal Bandits group. Concentrations (means +/- SD) of nicotine, NNN, NNK, and total TSNAs comparing the two major brand categories are as follows: nicotine--11.6 +/- 1.01 mg/g versus 6.96 +/- 3.62 mg/g (P = .0017), NNN--7.74 +/- 1.70 micrograms/g versus 4.17 +/- 1.35 micrograms/g (P < .0001), NNK--1.23 +/- 0.68 micrograms/g versus 0.61 +/- 0.41 micrograms/g (P = .0119), and total TSNAs--14.3 +/- 3.82 micrograms/g versus 6.3 +/- 2.56 micrograms/g (P < .0001). CONCLUSIONS The three leading U.S. snuff brands (Copenhagen, Skoal fine cut, and Kodiak; making up 92% of the U.S. market) showed not only high levels of pH, nicotine, and unprotonated (free) nicotine, but also high concentrations of the strongly carcinogenic TSNAs in comparison with the fourth and fifth best selling moist snuff brands, Hawken and Skoal Bandits (3% of the U.S. market).
Meta‐analysis of anthropogenic habitat disturbance effects on animal‐mediated seed dispersal

Anthropogenic habitat disturbance is a strong biodiversity change driver that compromises not only the species persistence but also the ecological interactions in which they are involved. Even though seed dispersal is a key interaction involved in the recruitment of many tree species and in consequence critical for biodiversity maintenance, studies assessing the effect of different anthropogenic disturbance drivers on this interaction have not been performed under a meta‐analytical framework. We assessed the way habitat fragmentation and degradation processes affect species diversity (abundance and species richness) and interaction rates (i.e., fruit removal and visitation rates) of different groups of seed‐disperser species at a global scale. We obtained 163 case studies from 37 articles. Results indicate that habitat degradation had a negative effect on seed‐disperser animal diversity, whereas habitat fragmentation had a negative effect on interaction rates. Birds and insects were more sensitive in terms of their diversity, whereas mammals showed a negative effect on interaction rates. Regarding habitat, both fragmentation and degradation had a negative effect on seed‐disperser animal diversity only in temperate habitats, and negative effects on interaction rates in tropical and temperate habitats. Our results indicate that the impact of human disturbance on seed‐disperser species and interactions is not homogeneous. On the contrary, the magnitude of effects seems to be dependent on the type of disturbance, taxonomic group under assessment, and geographical region where the human impact occurs.
Molecular Gene Profiling of Clostridium botulinum Group III and Its Detection in Naturally Contaminated Samples Originating from Various European Countries

ABSTRACT We report the development of real-time PCR assays for genotyping Clostridium botulinum group III targeting the newly defined C. novyi sensu lato group; the nontoxic nonhemagglutinin (NTNH)-encoding gene ntnh; the botulinum neurotoxin (BoNT)-encoding genes bont/C, bont/C/D, bont/D, and bont/D/C; and the flagellin (fliC) gene. The genetic diversity of fliC among C. botulinum group III strains resulted in the definition of five major subgroups named fliC-I to fliC-V. Investigation of fliC subtypes in 560 samples, with various European origins, showed that fliC-I was predominant and found exclusively in samples contaminated by C. botulinum type C/D, fliC-II was rarely detected, no sample was recorded as fliC-III or fliC-V, and only C. botulinum type D/C samples tested positive for fliC-IV. The lack of genetic diversity of the flagellin gene of C. botulinum type C/D would support a clonal spread of type C/D strains in different geographical areas. fliC-I to fliC-III are genetically related (87% to 92% sequence identity), whereas fliC-IV from C. botulinum type D/C is more genetically distant from the other fliC types (with only 50% sequence identity). These findings suggest fliC-I to fliC-III have evolved in a common environment and support a different genetic evolution for fliC-IV. A combination of the C. novyi sensu lato, ntnh, bont, and fliC PCR assays developed in this study allowed better characterization of C. botulinum group III and showed the group to be less genetically diverse than C. botulinum groups I and II, supporting a slow genetic evolution of the strains belonging to C. botulinum group III.
MATERNALLY EXPRESSED PAB C-TERMINAL, a Novel Imprinted Gene in Arabidopsis, Encodes the Conserved C-Terminal Domain of Polyadenylate Binding Proteins[W]

Parental imprinting is important for seed development, but few imprinted genes have been identified in plants. The four known imprinted genes in Arabidopsis thaliana encode transcriptional regulators. Here, we describe a novel imprinted gene, MATERNALLY EXPRESSED PAB C-TERMINAL (MPC), which encodes the C-terminal domain of poly(A) binding proteins (PABPs). PABPs play roles in mRNA stability and translation. MPC interacts with proteins that also interact with the C-terminal domain of typical PABPs, suggesting that MPC may regulate translation by modulating PABP activity. In the endosperm, MPC is expressed only from the maternal allele. Reduction of MPC expression affects seed development. In dna methyltransferase1 (met1) mutants, MPC is ectopically expressed, and the paternal allele is active in the endosperm. CGs in the 5′ flanking region and gene body of MPC lose methylation in a met1 background. Both regions are required to confer imprinted reporter expression, suggesting that the gene body contains imprinting control region elements. In Arabidopsis, DEMETER (DME) activates expression of maternal alleles. MPC expression is reduced in flowers and seeds in a dme-4 mutant but only after fertilization in dme-1. We conclude that other factors along with DME promote MPC expression and that DME has indirect effects on imprinted gene expression in endosperm.