Miracle-dz/UniFAR-FTUs huggingface dataset:
Ticagrelor enhances adenosine-mediated antiplatelet effect in acute coronary syndrome patients-a prospective cohort study

Background: Ticagrelor could exert a potential higher antiplatelet effect than clopidogrel and inhibit cellular uptake of adenosine, which was associated with several cardiovascular effects. We aimed to explore the association of plasma adenosine concentration (APC) and antiplatelet effect with clopidogrel or ticagrelor in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT). Methods: In this prospective, observational, and single-center cohort study, we enrolled 71 patients treated with ticagrelor and 85 with clopidogrel. We monitored the inhibition platelet aggregation (IPA) and assessed the adenosine and cyclic adenosine monophosphate (cAMP) plasma concentration. Clinical data and cardiovascular events of 30 days were also collected to investigate the differences between the groups and hazard ratios during prognosis. Results: The IPA of ticagrelor was significantly higher than clopidogrel (88.30 ± 13.06% vs. 60.02 ± 28.38%, P=0.001). The APC was significantly higher in ticagrelor therapy than clopidogrel therapy (2.88 ± 0.62 μmol/L vs. 2.56 ± 0.40 μmol/L, P=0.019). The cAMP plasma concentration was also significantly higher in ticagrelor therapy than clopidogrel therapy (21.91 ± 9.15 pmol/ml vs. 18.43 ± 9.02 pmol/ml, P=0.013). The plasma levels of adenosine and cAMP were positively correlated with ADP-induced IPA (r=0.68, P<0.001; r=0.30, P=0.002, respectively). The multivariate analysis adjusted for the dyspnea revealed that the treatment with ticagrelor was independently associated with this adverse drug reaction (odds ratio (OR), 5.295; 95% confidence interval (CI), 1.429-19.617). Conclusion: Results from this study indicated that ticagrelor could increase adenosine and cAMP plasma concentration and had a potential antiplatelet effect in patients with ACS that might be adenosine-mediated.
Forecasting Profitability and Earnings: A Study of the UK Stock Market (1982-2000)

An approach recently developed by Fama and French (2000) is applied to the study of whether UK company profitability is mean-reverting. A sample of roughly 987 firms per year for a period from 1982-2000 is used, drawn from Datastream. In a simple partial adjustment model convergence towards the mean at a rate of about 25% per year is found. The results are very similar in direction to those of Fama and French (2000) but the results do not display significant non-linearities. The change in profitability appears to be more strongly influenced by dividends in the UK.
Production of Anti‐idiotypic Antibodies as Potential Immunoreagents for the Serological Diagnosis of Bovine Cysticercosis

Although serological assays have been developed for cysticercosis, difficulties remain in isolating antigens from cross-reacting components and in obtaining reliable sources of parasite material for purification. The object of this study was to demonstrate the feasibility of using anti-idiotypic antibodies as alternative immunoreagents for the serological diagnosis of bovine cysticercosis. A fraction of Taenia hydatigena cyst fluid (ThFAS) had previously been used as a diagnostic antigen for Taenia saginata cysticercosis. Rabbits and mice were inoculated with ThFAS to produce either polyclonal or monoclonal antibodies (idiotypes), respectively. Idiotypes were purified by preparative protein A column, then inoculated into other rabbits to produce anti-idiotypes. The presence of anti-idiotypes in hyperimmune serum was demonstrated by competitive inhibition ELISA. Then anti-idiotypes were purified and used as coating antigen in a plate ELISA; results were compared to those using ThFAS as coating antigen. Anti-idiotypes yielded results comparable to those obtained with the native antigen and thus can be used as synthetic antigens for diagnostic purposes.
Relative accuracy of the halothane challenge test and a molecular genetic test in detecting the gene for porcine stress syndrome.

Pietrain swine homozygous for the hal gene (n) associated with porcine stress syndrome (PSS) and a Pietrain-derivative breed, Near Pietrain (NP), with a frequency of . 31 for n, were mated to produce reciprocal F1, F2, and purebred NP litters. The halothane challenge test was performed on all 40 parents and 240 progeny to predict their hal genotype and PSS susceptibility. The DNA-based assay for a C to T mutation at base pair 1,843 of the skeletal muscle ryanodine receptor (ryr1) cDNA, which is very highly correlated with PSS, was also determined for these animals. The predicted hal genotypes observed in the progeny differed significantly from the expected Mendelian ratios, and the halothane challenge test consistently overestimated the n/n hal genotype. However, the ryr1 genotypes observed in the progeny did not differ significantly from the expected Mendelian ratios, and this DNA-based assay apparently misidentified only one of the 40 parents. The results of this study indicate that the assay for the ryr1 mutation more accurately predicts both the homozygous and heterozygous forms of the PSS gene than does the halothane challenge test.
Uncompetitive Inhibition of Xenopus laevis Aldehyde Dehydrogenase 1A1 by Divalent Cations

Abstract Aldehyde dehydrogenases (ALDHs) convert aldehydes into their corresponding carboxylic acids. ALDH1A1, also known as ALDH class 1 (ALDH1) or retinaldehyde dehydrogenase (RALDH1), prefers retinal to acetaldehyde as a substrate. To investigate the effects of divalent cations on the dehydrogenase activity of Xenopus laevis ALDH1A1, the formation of acetate and retinoic acid from acetaldehyde and retinal, respectively, was investigated in the presence of Ca2+, Mg2+, Mn2+ or Zn2+. All divalent cations tested inhibited the oxidation of acetaldehyde and retinal by ALDH1A1. When acetaldehyde was used as a substrate, the 50% inhibitory concentrations (IC50) were 10, 24, 35 and 220 μM for Zn2+, Mn2+, Mg2+ and Ca2+, respectively. Kinetic studies of ALDH1A1 dehydrogenase activity in the presence or absence of each cation revealed that the inhibition mode by cations was uncompetitive against acetaldehyde, retinal, and NAD+, and that their inhibitory potencies were greater against acetaldehyde than retinal. It was concluded that the divalent cations inhibited X. laevis ALDH1A1 activity in a substrate-dependent manner by affecting a step of the dehydrogenase reaction that occurred after the formation of the ternary complex of the enzyme, substrate, and coenzyme.
Calpain‐mediated activation of NO synthase in human neuroblastoma SK‐N‐BE cells

In resting human neuronal cells, nitric oxide synthase (nNOS) is present in its native 160 kDa form in a quiescent state predominantly co‐localized on the plasma membrane, via its PDZ (Psd‐95/Discs‐large/Zona Occludens) domain, with NMDA receptor (NMDA‐R) and in tight association with heat shock protein 90 (HSP90). Following exposure of the cells to Ca2+‐ionophore or to NMDA, nNOS undergoes proteolytic removal of the PDZ domain being converted into a fully active 130 kDa form. The newly generated nNO synthase form dissociates from NMDA‐R and extensively diffuses into the cytosol in direct correlation with NO production. Intracellular redistribution and activation of nNOS are completely prevented in cells preloaded with calpain inhibitor‐1, indicating that these processes are triggered by a concomitant activation of calpain. The role of calpain has been confirmed by immunoprecipitation experiments revealing that also μ‐calpain is specifically recruited into the NMDA‐R‐nNOS‐HSP90 complex following calcium loading. Thus, the formation of clusters containing HSP90, μ‐calpain, nNOS and NMDA‐R represents the limiting step for the operation of the mechanism that links an efficient synthesis of NO to a local increase in Ca2+ influx.
The CACC Box and Myocyte Enhancer Factor-2 Sites within the Myosin Light Chain 2 Slow Promoter Cooperate in Regulating Nerve-specific Transcription in Skeletal Muscle*

Previous experiments showed that activity of the −800-base pair MLC2slow promoter was 75-fold higher in the innervated soleus (SOL) compared with the noninnervated SOL muscles. Using in vivo DNA injection of MLC2slow promoter-luciferase constructs, the aim of this project was to identify regulatory sites and potential transcription factors important for slow nerve-dependent gene expression. Three sites within the proximal promoter (myocyte enhancer factor-2 (MEF2), E-box, and CACC box) were individually mutated, and the effect on luciferase expression was determined. There was no change in luciferase expression in the SOL and extensor digitorum longus (EDL) muscles when the E-box was mutated. In contrast, the MEF2 mutation resulted in a 30-fold decrease in expression in the innervated SOL muscles (10.3 versus 0.36 normalized relative light units (RLUs)). Transactivation of theMLC2slow promoter by overexpressing MEF2 was only seen in the innervated SOL (676,340 versus 2,225,957 RLUs;p < 0.01) with no effect in noninnervated SOL or EDL muscles. These findings suggest that the active MLC2slowpromoter is sensitive to MEF2 levels, but MEF2 levels alone do not determine nerve-dependent expression. Mutation of the CACC box resulted in a significant up-regulation in the EDL muscles (0.23versus 4.08 normalized RLUs). With the CACC box mutated, overexpression of MEF2 was sufficient to transactivate the MLC2slow promoter in noninnervated SOL muscles (27,536 versus1,605,797 RLUs). Results from electrophoretic mobility shift and supershift assays confirm MEF2 protein binding to the MEF2 site and demonstrate specific binding to the CACC sequence. These results suggest a model for nerve-dependent regulation of theMLC2slow promoter in which derepression occurs through the CACC box followed by quantitative expression through enhanced MEF2 activation.
Factors that predict intrahepatic recurrence of hepatocellular carcinoma in 81 patients initially treated by percutaneous ethanol injection

In Japan, where liver transplantation has not been used to treat patients with hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) has been employed for those with small HCCs that are not amenable to surgical resection. In the current study, the authors evaluated PEI as a treatment for HCC patients by studying recurrence rates and survival after treatment. They then examined the clinicopathologic factors that predicted patterns of local and distant intrahepatic recurrence.
Predominant information transfer from layer III pyramidal neurons to corticospinal neurons

Connections of layer III pyramidal neurons to corticospinal neurons of layer V and corticothalamic neurons of layer VI in the rat primary motor cortex were examined in brain slices by combining intracellular staining with Golgi‐like retrograde labeling of corticofugal neurons. Forty layer III pyramidal neurons stained intracellularly were of the regular‐spiking type, showed immunoreactivity for glutaminase, and emitted axon collaterals arborizing locally in layers II/III and/or V. Nine of them were reconstructed for morphologic analysis; 15.2% or 3.8% of varicosities of axon collaterals of the reconstructed neurons were apposed to dendrites of corticospinal or corticothalamic neurons, respectively. By confocal laser scanning and electron microscopy, some of these appositions were revealed to make synapses. These findings suggest that corticospinal neurons receive information from the superficial cortical layers four times more frequently than corticothalamic neurons. The connections were further examined by intracellular recording of excitatory postsynaptic potential (EPSP) that were evoked in layer V and layer VI pyramidal neurons by stimulation of layer II/III. EPSPs evoked in layer V pyramidal neurons showed short and constant onset latencies, suggesting their monosynaptic nature. In contrast, most EPSPs evoked in layer VI pyramidal neurons had long onset latencies, showed double‐shock facilitation of onset latency, and were largely suppressed by an N‐methyl‐D‐aspartic acid receptor blocker, suggesting that they were polysynaptic. The results suggest that information from the superficial cortical layers is transferred directly and efficiently to corticospinal neurons in layer V and thereby exerts an important influence on cortical motor output. Corticothalamic neurons are, in contrast, considered relatively independent of, or indirectly related to, information processing of the superficial cortical layers. J. Comp. Neurol. 423:52–65, 2000. © 2000 Wiley‐Liss, Inc.
Polyamine Depletion Increases Cytoplasmic Levels of RNA-binding Protein HuR Leading to Stabilization of Nucleophosmin and p53 mRNAs*

Polyamines are essential for maintaining normal intestinal epithelial integrity, an effect that relies, at least in part, on their ability to keep low levels of nucleophosmin (NPM) and p53 mRNAs. The RNA-binding protein HuR associates with the p53 mRNA, as reported previously, and with the NPM mRNA, computationally predicted to be a target of HuR. Here, we show that HuR binds the NPM and p53 3′-untranslated regions and stabilizes these mRNAs in polyamine-depleted intestinal epithelial cells. Depletion of cellular polyamines by inhibiting ornithine decarboxylase with α-difluoromethylornithine dramatically enhanced the cytoplasmic abundance of HuR, whereas ectopic ornithine decarboxylase overexpression decreased cytoplasmic HuR; neither intervention changed whole-cell HuR levels. HuR was found to specifically bind the 3′-untranslated regions of NPN and p53 mRNAs. HuR silencing rendered the NPM and p53 mRNAs unstable and prevented increases in NPM and p53 mRNA and protein in polyamine-deficient cells. These results indicate that polyamines modulate cytoplasmic HuR levels in intestinal epithelial cells, in turn controlling the stability of the NPM and p53 mRNAs and influencing NPM and p53 protein levels.
Effects of Surgical Levels of Propofol and Sevoflurane Anesthesia on Cerebral Blood Flow in Healthy Subjects Studied with Positron Emission Tomography

Background The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis. Methods Using H215O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC50, or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 &mgr;g/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation. Results Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36–53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7–16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62–70%, with minor further effects. In the SPM analysis of the “awake to 1 MAC/EC50” step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices. Conclusions Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC50 level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases.
Grade repetition: A comparative study of academic and non-academic consequences

This article explores country-by-country differences in academic performance and attitudes towards school between students who repeated a grade in primary school, in secondary school or never repeated a grade. The analyses use PISA 2009 for 30 countries in which a relatively high proportion of students repeated a grade before the age of 15. The comparisons across countries and the examination of models of both academic and non-academic performance contribute to shed some light on the consequences of repeating a grade for students. The estimated associations suggest that in most countries examined, at the age of 15, students who repeated a grade in secondary school tend to perform better academically than do students who repeated a grade in primary school, but worse than non-repeaters. In terms of the measure of behavioural performance chosen for this analysis, attitudes towards school, in the majority of countries, non-repeaters tend to report more positive attitudes towards schools than primary and secondary-school repeaters, but the comparison between repeaters in primary and secondary schools shows less consistent patterns across countries. These differences are observed after accounting for background characteristics of the students and exploring some differential relationships between grade repetition and education outcomes according to student characteristics. The achievement and behavioural gaps among groups of repeaters may reflect differences in the development of academic and behavioural skills over the school years, as well as differences in the way these groups of students are treated across different educational systems.
Suicidality in adolescents and adults with binge‐eating disorder: Results from the national comorbidity survey replication and adolescent supplement

OBJECTIVE The relation between binge-eating disorder (BED) and suicidality (i.e., suicide ideation, plan, and/or attempt) has not been studied extensively, and it is unknown whether BED is uniquely associated with suicidality when adjusting for comorbid psychopathology. Moreover, the course of suicidality in BED has not been determined and it is unknown whether BED precedes suicidality or vice versa. METHOD A total of 10,123 adolescents and 2,980 adults from two nationally representative surveys were administered diagnostic interviews assessing psychopathology and suicidality, as well the retrospectively reported ages of onset. RESULTS Among adults and adolescents, BED was associated with elevated odds of suicide ideation, plan, and attempt at a univariate level, but BED was not associated with elevated odds of suicidality when adjusting for comorbid psychopathology. Kaplan-Meier estimates of temporal patterns displayed that most adolescents experienced suicidality onset following BED onset, whereas most adults experienced suicidality onset prior to BED onset. DISCUSSION BED, comorbid disorders, and suicidality share common factors and interrelations, and individuals with BED and comorbid disorders may be at particularly high risk for suicidal outcomes. The presence of BED in adolescence may serve as a marker for more severe symptomatology that precedes the occurrence of suicidality. Research is needed to understand how eating disorder symptoms, comorbid symptoms, and suicidality affect one another over time. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:40-49).
The Valuation of Composite Investment Instruments

The return on composite investment instruments takes the form of weighted-average, derived from the performance of at least two economic indicators. Three allocation experiments illustrate that prospective investors tend to valuate composites "by-tranche", consistently violating the rational premise of reduction. Valuation-by-tranche shows for uncertain and risky composites, and reflects in allocation problems and binary choice. The willingness to invest in a given composite still strongly increases when one tranche hedges against the other, suggesting that reduced-form considerations might interfere with the inclination to value components separately. A hybrid model where investors weight the values of underlying tranches, but also respond to the reduced-form prospect, approximates the data most accurately. Personal tendency to valuate composites by-tranche negatively correlates with choice consistency, suggesting that component-level processing might bias investment decision and open space for profitable composite engineering.
EDContours: High-Speed Parameter-Free Contour Detector Using EDPF

We present a high-speed contour detector, which we name EDContours, that works by running our real-time parameter-free edge segment detector, Edge Drawing Parameter Free (EDPF), at different scale-space representations of an image. Combining the edge segments detected by EDPF at different scales, EDContours generates a soft contour map for a given image. EDContours works on gray-scale images, is parameter-free, runs very fast, and results in an F-measure score of 0.62 on the Berkeley Segmentation Dataset (BSDS300).
Environment and Economy: Property Rights and Public Policy

Property, rights, and property rights property rights and property regimes in natural resource policy entitlements by property rules, liability rules, and inalienability rules property rights and externalities property rights, missings markets, and environmental uncertainty the tradegy of the commons property rights problems in the public domain private property, public property, and social preferences private property rights and presumptive policy entitlements the policy problem - ideology, effeciency, and objective truth rules.
Influence of the Natural Microbial Flora on the Acid Tolerance Response of Listeria monocytogenes in a Model System of Fresh Meat Decontamination Fluids

ABSTRACT Depending on its composition and metabolic activity, the natural flora that may be established in a meat plant environment can affect the survival, growth, and acid tolerance response (ATR) of bacterial pathogens present in the same niche. To investigate this hypothesis, changes in populations and ATR of inoculated (105 CFU/ml)Listeria monocytogenes were evaluated at 35°C in water (10 or 85°C) or acidic (2% lactic or acetic acid) washings of beef with or without prior filter sterilization. The model experiments were performed at 35°C rather than lower (≤15°C) temperatures to maximize the response of inoculated L. monocytogenes in the washings with or without competitive flora. Acid solution washings were free (<1.0 log CFU/ml) of natural flora before inoculation (day 0), and no microbial growth occurred during storage (35°C, 8 days). Inoculated L. monocytogenes died off (negative enrichment) in acid washings within 24 h. In nonacid (water) washings, the pathogen increased (approximately 1.0 to 2.0 log CFU/ml), irrespective of natural flora, which, when present, predominated (>8.0 log CFU/ml) by day 1. The pH of inoculated water washings decreased or increased depending on absence or presence of natural flora, respectively. These microbial and pH changes modulated the ATR of L. monocytogenes at 35°C. In filter-sterilized water washings, inoculated L. monocytogenes increased its ATR by at least 1.0 log CFU/ml from days 1 to 8, while in unfiltered water washings the pathogen was acid tolerant at day 1 (0.3 to 1.4 log CFU/ml reduction) and became acid sensitive (3.0 to >5.0 log CFU/ml reduction) at day 8. These results suggest that the predominant gram-negative flora of an aerobic fresh meat plant environment may sensitize bacterial pathogens to acid.