Miracle-dz/UniFAR-FTUs huggingface dataset:
Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis

Introduction Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2gt/gt) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters. Material and methods We performed long-term-ECG recordings in transgenic CAP2 deficient mice (C57BL/6) to detect spontaneous arrhythmias. In vivo electrophysiological studies by right heart catheterization and ex vivo epicardial mapping were used to analyze electrophysiological parameters, the inducibility of arrhythmias, and conduction velocities. Expression and distribution of cardiac connexins and the amount of cardiac fibrosis were evaluated. Results Spontaneous ventricular arrhythmias could be detected in Cap2gt/gt during the long-term-ECG recording. Cap2gt/gt showed marked conduction delays at atrial and ventricular levels, including a reduced heart rate (421.0 ±40.6 bpm vs. 450.8 ±27.9 bpm; p < 0.01), and prolongations of PQ (46.3 ±4.1 ms vs. 38.6 ±6.5 ms; p < 0.01), QRS (16.2 ±2.6 ms vs. 12.6 ±1.4 ms; p < 0.01), and QTc interval (55.8 ±6.0 ms vs. 45.2 ±3.3 ms; p = 0.02) in comparison to wild type mice. The PQ prolongation was due to an infra-Hisian conduction delay (HV: 9.7 ±2.1 ms vs. 6.5 ±3.1 ms; p = 0.02). The inducibility of ventricular tachycardias during the electrophysiological studies was significantly elevated in the mutant mice (inducible animals: 88% vs. 33%; p = 0.04). Cap2gt/gt showed more abnormal distribution of connexin43 compared to WT (23.0 ±4.7% vs. 2.9 ±0.8%; p < 0.01). Myocardial fibrosis was elevated in Cap2gt/gt hearts (9.1 ±6.7% vs. 5.5 ±3.3%; p < 0.01). Conclusions Loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in Cap2gt/gt are associated with alterations in myocardial connexins and fibrosis.
Extraction of Glycyrrhizic Acid and Glabridin from Licorice

The extraction and separation conditions of glycyrrhizic acid and glabridin from licorice were investigated. By changing the different extraction solvents, procedures, times and temperature, the optimum extraction condition was established: the used of ethanol/water (30:70, v/v) as an extraction solvent, and 60 min dipping time under 50°C. The extracts of licorice were separated and determined by reversed-phase high performance liquid chromatography with a methanol/water (70:30, v/v, containing 1% acetic acid) as the mobile phase. Under the optimum extraction condition, 2.39 mg/g of glycyrrhizic acid and 0.92 mg/g of glabridin were extracted from Chinese licorice and the recoveries were 89.7% and 72.5% respectively.
Optimisation de la microstructure d'aciers ferrito-martensitiques à 3.5 % pds Mn : des transformations de phases à la micro-mécanique

Les aciers Dual-Phase sont largement utilises dans le secteur de l’automobile enraison de leurs proprietes mecaniques remarquables et du bon compromis resistanceductilite qui lui donne d’interessante potentialites comme absorbeur d’energiemecanique. Cependant, la recherche de bons compromis entre les proprietesmecaniques en traction et celles de formabilite necessite une optimisation desparametres microstructuraux. Ce travail de these s’inscrit dans cet optique. Dans unepremiere partie, l’etude bibliographique proposee permet de mieux cerner lesparametres influencant la formation des microstructures ainsi que les proprietes desaciers DP. Dans une seconde partie, nous proposons un travail experimental originalpermettant de mieux comprendre la formation des microstructures des aciers DP etde decoupler l’effet de certains parametres microstructuraux sur les proprietes deces aciers. Enfin, la modelisation micromecanique proposee permet de completer etd’interpreter les donnees experimentales acquises. Ce travail ouvre des voiesinteressantes de « design » des microstructures des aciers DP en vue de developperdes aciers de nouvelles generations possedant des proprietes optimisees.
Response of Kalanchoe daigremontiana to wounding and infection with Agrobacterium tumefaciens

Background and Purpose: Transformation of plant tissue with Agrobacterium tumefaciens includes wounding of plant and subsequent infection by bacteria. Polyphenol oxidase activity and oxidative stress parameters – the content of H2O2, as well as activity and isoenzymes of antioxidative enzymes catalase, pyrogallol and guaiacol peroxidase were investigated as markers of plant response to wounding and infection. Materials and Methods: Five tissue types – healthy tissue, wounded tissue, tissue in immediate proximity of the wound, tumour tissue and tissue next to the tumour were collected on 7, 14 and 21 day after wounding or infection. Activities of antioxidative enzymes were evaluated spectrophotometrically. Isoenzymes were separated electrophoretically in native conditions. H2O2 content was estimated by measuring the titanium hydro-peroxide complex. Results and Conclusion: All measured parameters were remarkably different in tumour in comparison to healthy tissue. Activities of peroxidases were significantly increased, accompanied with induction of new isoenzymes. After two weeks of the experiment catalase activity was also significantly increased in tumour tissue as well as in tissue next to the wound. H2O2 content was lower in tumour after three weeks. Aside from tumour tissue, polyphenol oxidase activity was significantly increased in tissue next to the tumour. Remarkably increased peroxidase and polyphenol oxidase activity in tumour tissue, additional isoenzymes of peroxidases as well as decreased H2O2 content, indicated changes in tissue organisation and induction of defence mechanisms against pathogen, in which these two groups of enzymes are involved. Wounded tissue, as well as tissue next to the wound or infection, did not show significant variation from healthy tissue.
2′Halo‐ATP and ‐GTP analogues: Rational phasing tools for protein crystallography

The solution of the crystallographic macromolecular phase problem requires incorporation of heavy atoms into protein crystals. Several 2′‐halogenated nucleotides have been reported as potential universal phasing tools for nucleotide binding proteins. However, only limited data are available dealing with the effect of 2′‐substitution on recognition by the protein. We have determined equilibrium dissociation constants of 2′‐halogenated ATP analogues for the ATP binding proteins UMP/CMP kinase and the molecular chaperone DnaK. Whereas the affinities to UMP/CMP kinase are of the same order of magnitude as for unsubstituted ATP, the affinities to DnaK are drastically decreased to undetectable levels. For 2′‐halogenated GTP analogues, the kinetics of interaction were determined for the small GTPases p21ras (Y32W) (fluorescent mutant) and Rab5. The rates of association were found to be within about one order of magnitude of those for the nonsubstituted nucleotides, whereas the rates of dissociation were accelerated by factors of ˜100 (p21ras) or ˜105 (Rab5), and the resulting equilibrium dissociation constants are in the nm or μM range, respectively. The data demonstrate that 2′halo‐ATP and ‐GTP are substrates or ligands for all proteins tested except the chaperone DnaK. Due to the very high affinities of a large number of GTP binding proteins to guanine nucleotides, even a 105‐fold decrease in affinity as observed for Rab5 places the equilibrium dissociation constant in the μM range, so that they are still well suited for crystallization of the G‐protein:nucleotide complex.
Individual Recognition in Domestic Cattle (Bos taurus): Evidence from 2D-Images of Heads from Different Breeds

Background In order to maintain cohesion of groups, social animals need to process social information efficiently. Visual individual recognition, which is distinguished from mere visual discrimination, has been studied in only few mammalian species. In addition, most previous studies used either a small number of subjects or a few various views as test stimuli. Dairy cattle, as a domestic species allow the testing of a good sample size and provide a large variety of test stimuli due to the morphological diversity of breeds. Hence cattle are a suitable model for studying individual visual recognition. This study demonstrates that cattle display visual individual recognition and shows the effect of both familiarity and coat diversity in discrimination. Methodology/Principal Findings We tested whether 8 Prim'Holstein heifers could recognize 2D-images of heads of one cow (face, profiles, ¾ views) from those of other cows. Experiments were based on a simultaneous discrimination paradigm through instrumental conditioning using food rewards. In Experiment 1, all images represented familiar cows (belonging to the same social group) from the Prim'Holstein breed. In Experiments 2, 3 and 4, images were from unfamiliar (unknown) individuals either from the same breed or other breeds. All heifers displayed individual recognition of familiar and unfamiliar individuals from their own breed. Subjects reached criterion sooner when recognizing a familiar individual than when recognizing an unfamiliar one (Exp 1: 3.1±0.7 vs. Exp 2: 5.2±1.2 sessions; Z = 1.99, N = 8, P = 0.046). In addition almost all subjects recognized unknown individuals from different breeds, however with greater difficulty. Conclusions/Significance Our results demonstrated that cattle have efficient individual recognition based on categorization capacities. Social familiarity improved their performance. The recognition of individuals with very different coat characteristics from the subjects was the most difficult task. These results call for studies exploring the mechanisms involved in face recognition allowing interspecies comparisons, including humans.
Size Scale and Defect Engineered Nanostructures for Optimal Strength and Toughness

Abstract : The goal of this research project was to develop realistic combinations of ceramics and/or semiconductors that simultaneously achieve high hardness (>40 GPa) and toughness (>400 MPa*m1/2). While this is probably unrealistic for bulk material production due to inherent defects associated with processing, there is a very real opportunity for thin coatings in environments involving severe wear and/or dynamic penetration. This includes a wide range of industrial applications, including automotive, aircraft, electronics, manufacturing, and biomedical. To achieve this goal, the proposal outlined three primary objectives: (1) the development of physically based, dislocation models to understand the deformation of brittle materials, (2) the synthesis of model ceramic nanocomposites that demonstrate high hardness and toughness, and (3) the detailed understanding of the arrangements and types of dislocation structures in small volumes. This involved the uniaxial compression of Si nanovolumes (spheres and towers) using a combination of TEM in situ indentation and molecular dynamics simulations for objective (1), the deposition of Si-SiC core-shell nanotowers for objective (2), and the HR TEM analysis of deformed Si nanovolumes for objective (3). This report summarizes the substantial progress made on the first two of these objectives and the work that is currently underway to address objective (3).
Development and Initial Validation of the Back Pain Functional Scale

Study Design. A prospective repeated-measures design was applied. Objectives. To examine the measurement properties of the Back Pain Functional Scale (BPFS) and the Roland–Morris Questionnaire (RMQ) and to formulate hypotheses and sample size estimates for a subsequent comparison study. Summary of Background Data. Although there are numerous functional status measures for patients with low back pain, most have been conceived of and validated with a group rather than an individual patient as the unit of interest. Also, little has been done to formally compare—this includes the generation of a priori hypotheses, followed by statistical hypotheses testing—the many competing measures. Methods. Subjects were 77 patients with low back pain who were referred by physicians to 10 outpatient physical therapy clinics located in Canada and the United States. The questionnaires were administered at patients’ initial visits, within 48 hours of the initial visit, and at 1-, 2-, and 3-week follow-up visits. Reliability, cross-sectional validity, and longitudinal validity (sensitivity to change) coefficients were calculated. Results. Test–retest reliability estimates of 0.81 and 0.88 were obtained for the RMQ and BPFS, respectively. The measures demonstrated similar levels of cross-sectional validity. Correlations of 0.56 and 0.65 were noted between a prognostic rating of change and the RMQ and BPFS, respectively. The RMQ demonstrated a ceiling effect. Approximately 180 patients are needed for a subsequent head-to-head comparison study of the measures. Conclusions. The BPFS appears to have sound measurement properties, and a formal head-to-head comparison study with the RMQ is warranted.
Comparative Study of Novel Ratio Spectra and Isoabsorptive Point Based Spectrophotometric Methods: Application on a Binary Mixture of Ascorbic Acid and Rutin

This paper presents novel methods for spectrophotometric determination of ascorbic acid (AA) in presence of rutin (RU) (coformulated drug) in their combined pharmaceutical formulation. The seven methods are ratio difference (RD), isoabsorptive_RD (Iso_RD), amplitude summation (A_Sum), isoabsorptive point, first derivative of the ratio spectra (1DD), mean centering (MCN), and ratio subtraction (RS). On the other hand, RU was determined directly by measuring the absorbance at 358 nm in addition to the two novel Iso_RD and A_Sum methods. The work introduced in this paper aims to compare these different methods, showing the advantages for each and making a comparison of analysis results. The calibration curve is linear over the concentration range of 4–50 μg/mL for AA and RU. The results show the high performance of proposed methods for the analysis of the binary mixture. The optimum assay conditions were established and the proposed methods were successfully applied for the assay of the two drugs in laboratory prepared mixtures and combined pharmaceutical tablets with excellent recoveries. No interference was observed from common pharmaceutical additives.
New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in this rapidly aging society.
Combination Strategies for Semantic Role Labeling

This paper introduces and analyzes a battery of inference models for the problem of semantic role labeling: one based on constraint satisfaction, and several strategies that model the inference as a meta-learning problem using discriminative classifiers. These classifiers are developed with a rich set of novel features that encode proposition and sentence-level information. To our knowledge, this is the first work that: (a) performs a thorough analysis of learning-based inference models for semantic role labeling, and (b) compares several inference strategies in this context. We evaluate the proposed inference strategies in the framework of the CoNLL-2005 shared task using only automatically-generated syntactic information. The extensive experimental evaluation and analysis indicates that all the proposed inference strategies are successful - they all outperform the current best results reported in the CoNLL-2005 evaluation exercise - but each of the proposed approaches has its advantages and disadvantages. Several important traits of a state-of-the-art SRL combination strategy emerge from this analysis: (i) individual models should be combined at the granularity of candidate arguments rather than at the granularity of complete solutions; (ii) the best combination strategy uses an inference model based in learning; and (iii) the learning-based inference benefits from max-margin classifiers and global feedback.
In Vivo Performance of Genetically Encoded Indicators of Neural Activity in Flies

Genetically encoded fluorescent probes of neural activity represent new promising tools for systems neuroscience. Here, we present a comparative in vivo analysis of 10 different genetically encoded calcium indicators, as well as the pH-sensitive synapto-pHluorin. We analyzed their fluorescence changes in presynaptic boutons of the Drosophila larval neuromuscular junction. Robust neural activity did not result in any or noteworthy fluorescence changes when Flash-Pericam, Camgaroo-1, and Camgaroo-2 were expressed. However, calculated on the raw data, fractional fluorescence changes up to 18% were reported by synapto-pHluorin, Yellow Cameleon 2.0, 2.3, and 3.3, Inverse-Pericam, GCaMP1.3, GCaMP1.6, and the troponin C-based calcium sensor TN-L15. The response characteristics of all of these indicators differed considerably from each other, with GCaMP1.6 reporting high rates of neural activity with the largest and fastest fluorescence changes. However, GCaMP1.6 suffered from photobleaching, whereas the fluorescence signals of the double-chromophore indicators were in general smaller but more photostable and reproducible, with TN-L15 showing the fastest rise of the signals at lower activity rates. We show for GCaMP1.3 and YC3.3 that an expanded range of neural activity evoked fairly linear fluorescence changes and a corresponding linear increase in the signal-to-noise ratio (SNR). The expression level of the indicator biased the signal kinetics and SNR, whereas the signal amplitude was independent. The presented data will be useful for in vivo experiments with respect to the selection of an appropriate indicator, as well as for the correct interpretation of the optical signals.
Developmental Effects of Exposures to Environmental Factors: The Polish Mother and Child Cohort Study

This paper estimates the effects of exposure to environmental factors, including lead, mercury, environmental tobacco smoke (ETS), and polycyclic aromatic hydrocarbons (PAH), on child psychomotor development. The study population consists of mother-child pairs in the Polish Mother and Child Cohort Study. Prenatal and postnatal exposure to environmental factors was determined from biomarker measurements as follows: for lead exposure—cord blood lead level, for mercury—maternal hair mercury level, for ETS—cotinine level in saliva and urine, and for PAH—1-hydroxypyrene (1-HP) in urine. At the age of 12 (406 subjects) and 24 months (198 subjects) children were assessed using Bayley Scales of Infant and Toddler Development. There were no statistically significant effects of prenatal exposure to mercury or 1-HP on child psychomotor development. After adjusting for potential confounders, adverse effects of prenatal exposure to ETS on motor development (β = −2.6; P = 0.02) and postnatal exposure to ETS on cognitive (β = −0.2; P = 0.05) and motor functions (β = −0.5; P = 0.01) were found. The adverse effect of prenatal lead exposure on cognitive score was of borderline significance (β = −6.2; P = 0.06). The study underscores the importance of policies and public health interventions that aim to reduce prenatal and postnatal exposure to lead and ETS.
Regulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106-01 osteoblast-like cells.

BACKGROUND Homologous down-regulation/desensitization of the parathyroid hormone receptor (PTH1R)/adenylate cyclase system has been demonstrated in uremia, and may contribute to parathyroid hormone (PTH) resistance; however, additional studies have shown that parathyroidectomy fails to normalize the down-regulation of the PTH1R. The present studies were designed to test directly, in vitro, the hypothesis that factors circulating in the uremic environment, other than PTH, decrease the response of osteoblastic cells to PTH. METHODS Studies were conducted in confluent cultures of UMR 106-01 osteoblast-like cells. Uremic ultrafiltrate (UUF) was obtained from patients on hemodialysis. Cells were exposed to media containing 50% uremic ultrafiltrate for periods of up to 72 hours. Control cultures were exposed to a buffered salt solution containing a comparable ionic composition to that of the UUF. PTH-stimulated cyclic adenosine monophosphate (cAMP) generation was determined by radioimmunoassay (RIA), PTH binding and PTH1R mRNA levels were determined by radioligand binding and Northern analysis, respectively. RESULTS PTH-stimulated cAMP generation from cultures treated with uremic ultrafiltrate for 48 hours was 1385.8 +/- 183.2 pmol/culture/5 minutes, whereas control cultures generated 2389.5 +/- 271 pmol cAMP/culture/5 minutes (P < 0.05). PTH binding was decreased by 30% in cultures incubated with UUF as compared to controls. The decrease in binding induced by UUF was accompanied by a decrease in PTH1R mRNA levels. CONCLUSION These findings demonstrate that factors present in UUF decrease PTH-stimulated cAMP generation by a mechanism that involves a decrease in the levels of PTH1R mRNA levels. Thus, the skeletal resistance to PTH in the setting of chronic kidney disease, may be explained, at least in part, by circulating factors other than PTH.