Miracle-dz/UniFAR-FTUs huggingface dataset:
Lomofungin and dilomofungin: inhibitors of MBNL1-CUG RNA binding with distinct cellular effects

Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disorder resulting from expression of RNA containing an expanded CUG repeat (CUGexp). The pathogenic RNA is retained in nuclear foci. Poly-(CUG) binding proteins in the Muscleblind-like (MBNL) family are sequestered in foci, causing misregulated alternative splicing of specific pre-mRNAs. Inhibitors of MBNL1-CUGexp binding have been shown to restore splicing regulation and correct phenotypes in DM1 models. We therefore conducted a high-throughput screen to identify novel inhibitors of MBNL1-(CUG)12 binding. The most active compound was lomofungin, a natural antimicrobial agent. We found that lomofungin undergoes spontaneous dimerization in DMSO, producing dilomofungin, whose inhibition of MBNL1–(CUG)12 binding was 17-fold more potent than lomofungin itself. However, while dilomofungin displayed the desired binding characteristics in vitro, when applied to cells it produced a large increase of CUGexp RNA in nuclear foci, owing to reduced turnover of the CUGexp transcript. By comparison, the monomer did not induce CUGexp accumulation in cells and was more effective at rescuing a CUGexp-induced splicing defect. These results support the feasibility of high-throughput screens to identify compounds targeting toxic RNA, but also demonstrate that ligands for repetitive sequences may have unexpected effects on RNA decay.
Effects of majority members' positive intergroup contact on minority members' support for ingroup rights: Mobilizing or demobilizing effects?

While some research suggests that ethnic and cultural diversity hinders societal cohesion, other studies show that it promotes intergroup contact opportunities, which, if exploited, help to overcome intergroup prejudice. Recently, however, intergroup contact theory has been criticized for neglecting the wider social context as well as for ignoring potential demobilizing contact effects for minority members. Using two cross-sectional general population surveys (European Social Survey in 22 countries, Swiss MOSAiCH), we address these criticisms by examining whether ethnic majority members' positive contact influences ethnic minority members' support for ingroup rights at the social context level. Applying multilevel path analysis, we show that minority members are more likely to support anti-discrimination laws and immigrant rights when living in social contexts in which majority members have positive intergroup contact experiences. Theoretical and practical implications of our findings are discussed for understanding how minority groups are affected by the climate of the social context they reside in.
Social-cognitive predictors of dietary behaviors in South Korean men and women

Background: Eating a diet that is high in vitamins and low in fat is considered to be governed by social-cognitive factors, such as intentions, planning, self-efficacy, and outcome expectancies. Purpose: A longitudinal field study was designed to examine the interrelationships of these factors with dietary behaviors. Method: In 697 South Korean men and women, objective health-risk status was assessed at Time 1 (cholesterol, blood pressure, and body mass index) in conjunction with self-efficacy, outcome expectancies, and intentions. At Time 2, six months later, coping self-efficacy, planning, and dietary behaviors were measured. A two-group structural equation model for men and women was specified to determine the relations of distal and proximal predictors of a healthy diet. Results: Self-efficacy was of equal predictive power in men and women, whereas intentions and planning were relevant only in women. Objective risk status was associated with intentions in women but not in men. Conclusions: Results confirm the predictive power of the Health Action Process Approach and point to the role of gender in the self-regulation of dietary behaviors.
The Effects of Contrast and Contrast Adaptation on Static 1 Receptive Field Features in Macaque Area V1. 2 3

1/47 The effects of contrast and contrast adaptation on static 1 receptive field features in macaque area V1. 2 3 Jean-Baptiste Durand, Pascal Girard, Pascal Barone, Jean Bullier, Lionel G. Nowak 4 5 Centre de Recherche Cerveau et Cognition, Université Toulouse 3-CNRS, Toulouse, France 6 7 8 9 Corresponding author: LG Nowak (lionel.nowak@cerco.ups-tlse.fr) 10 11 12 13 Authors' Contributions 14 LGN conceived the experiment. PG, PB, JB and LGN performed the experiments. JDB analyzed the 15 data. LGN wrote the manuscript. 16 17 Articles in PresS. J Neurophysiol (July 18, 2012). doi:10.1152/jn.00936. 2011
Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma

The prognostic values of IRF-1 and Ki-67 for liver transplantation (LT) of hepatocellular carcinoma (HCC) were investigated, as well as the mechanisms of IRF-1 in tumor suppression. Adult orthotropic liver transplantation cases (N = 127) were involved in the analysis. A significant decreased recurrence free survival (RFS) was found in the Ki-67 positive groups. Ki-67, tumor microemboli, the Milan and UCSF criteria were found to be independent risk factors for RFS. In LT for HCC beyond the Milan criteria, a significant decrease in RFS was found in the IRF-1 negative groups. In SK-Hep1 cells, an increase in apoptosis and decrease in autophagy were observed after IFN-γ stimulation, which was accompanied with increasing IRF-1 levels. When IRF-1 siRNA or a caspase inhibitor were used, reductions in LC3-II were diminished or disappeared after IFN-γ stimulation, suggesting that IFN-γ inhibited autophagy via IRF-1 expression and caspase activation. However, after IRF-1 siRNA was introduced, a reduction in LC3-II was found. Thus basic expression of IRF-1 was also necessary for autophagy. IRF-1 may be used as a potential target for HCC treatment based on its capacity to affect apoptosis and autophagy. Ki-67 shows great promise for the prediction of HCC recurrence in LT and can be used as an aid in the selection of LT candidates.
Prebiotics from Marine Macroalgae for Human and Animal Health Applications

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.
Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas

SUMMARY Hydrogen sulfide (H2S) has been proposed to mediate hypoxic vasoconstriction (HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H2S. Here we examined the relationship between H2S and O2 in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H2S (Na2S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries (EBA) but did not affect ventral aortas or afferent branchial arteries; effects similar to those produced by hypoxia. Sensitivity of H2S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H2S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H2S-synthesizing enzyme, cystathionine β-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine λ-lyase. Oxygen consumption (ṀO2) of hagfish DA was constant between 15 and 115 mmHg PO2 (1 mmHg=0.133 kPa), decreased when PO2 <15 mmHg, and increased after PO2 exceeded 115 mmHg. 10 μmol l–1 H2S increased and ⩾100μ mol l–1 H2S decreased ṀO2. Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased ṀO2. These results show that H2S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H2S was enhanced at low PO2, it is unlikely that H2S contractions are mediated by either H2S–NO interaction or an oxidation product of H2S. These experiments also provide additional support for the hypothesis that the metabolism of H2S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle.
Endothelium-Derived Hyperpolarizing Factor Determines Resting and Stimulated Forearm Vasodilator Tone in Health and in Disease

Background— We assessed the contribution of endothelium-derived hyperpolarizing factors to resting and agonist-stimulated vasodilator tone in health and disease. Tetraethylammonium chloride (TEA) was used to inhibit K+Ca channel activation and fluconazole was used to inhibit cytochrome P450 2C9–mediated epoxyeicosatrienoic acid synthesis. We hypothesized that endothelium-derived hyperpolarizing factors contribute to resting vascular tone by K+Ca channel activation and epoxyeicosatrienoic acid release and that endothelium-derived hyperpolarizing factors compensate for reduced nitric oxide bioavailability at rest and with endothelium-dependent vasodilators. Methods and Results— In 103 healthy subjects and 71 nonhypertensive subjects with multiple risk factors, we measured resting forearm blood flow (FBF) using venous occlusion plethysmography before and after intra-arterial infusions of NG-monomethyl-L-arginine (L-NMMA), TEA, fluconazole, and their combination. The effects of these antagonists on resting FBF and on bradykinin- and acetylcholine-mediated vasodilation were studied. Resting FBF decreased with TEA and L-NMMA in all subjects (P<0.001); however, the vasoconstrictor response to L-NMMA was greater (P=0.04) and to TEA was lower (P=0.04) in healthy subjects compared with those with risk factors. Fluconazole decreased resting FBF in all subjects, and the addition of TEA further reduced FBF after fluconazole, suggesting that cytochrome P450 metabolites and other hyperpolarizing factor(s) activate K+Ca channels. Both L-NMMA and TEA attenuated bradykinin-mediated vasodilation in healthy and hypercholesterolemic subjects (P<0.001). In contrast, acetylcholine-mediated vasodilation remained unchanged with TEA in healthy subjects but was significantly attenuated in hypercholesterolemia (P<0.04). Conclusions— First, by activating TEA-inhibitable K+Ca channels, endothelium-derived hyperpolarizing factors, together with nitric oxide, contribute to resting microvascular dilator tone. The contribution of K+Ca channel activation compared with nitric oxide is greater in those with multiple risk factors compared with healthy subjects. Second, activation of K+Ca channels is only partly through epoxyeicosatrienoic acid release, indicating the presence of other hyperpolarizing mechanisms. Third, bradykinin, but not acetylcholine, stimulates K+Ca channel–mediated vasodilation in healthy subjects, whereas in hypercholesterolemia, K+Ca channel-mediated vasodilation compensates for the reduced nitric oxide activity. Thus, enhanced endothelium-derived hyperpolarizing factor activity in conditions of nitric oxide deficiency contributes to maintenance of resting and agonist-stimulated vasodilation. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00166166.
Genetic Instability and Intratumoral Heterogeneity in Neuroblastoma with MYCN Amplification Plus 11q Deletion

Background/Aim Genetic analysis in neuroblastoma has identified the profound influence of MYCN amplification and 11q deletion in patients’ prognosis. These two features of high-risk neuroblastoma usually occur as mutually exclusive genetic markers, although in rare cases both are present in the same tumor. The purpose of this study was to characterize the genetic profile of these uncommon neuroblastomas harboring both these high-risk features. Methods We selected 18 neuroblastomas with MNA plus 11q loss detected by FISH. Chromosomal aberrations were analyzed using Multiplex Ligation-dependent Probe Amplification and Single Nucleotide Polymorphism array techniques. Results and Conclusion This group of tumors has approximately the same high frequency of aberrations as found earlier for 11q deleted tumors. In some cases, DNA instability generates genetic heterogeneity, and must be taken into account in routine genetic diagnosis.
Towards Real-time Simulation of Hyperelastic Materials

We present a new method for real-time physics-based simulation supporting many different types of hyperelastic materials. Previous methods such as Position Based or Projective Dynamics are fast, but support only limited selection of materials; even classical materials such as the Neo-Hookean elasticity are not supported. Recently, Xu et al. [2015] introduced new "spline-based materials" which can be easily controlled by artists to achieve desired animation effects. Simulation of these types of materials currently relies on Newton's method, which is slow, even with only one iteration per timestep. In this paper, we show that Projective Dynamics can be interpreted as a quasi-Newton method. This insight enables very efficient simulation of a large class of hyperelastic materials, including the Neo-Hookean, spline-based materials, and others. The quasi-Newton interpretation also allows us to leverage ideas from numerical optimization. In particular, we show that our solver can be further accelerated using L-BFGS updates (Limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm). Our final method is typically more than 10 times faster than one iteration of Newton's method without compromising quality. In fact, our result is often more accurate than the result obtained with one iteration of Newton's method. Our method is also easier to implement, implying reduced software development costs.
Complete search in test generation for industrial circuits with improved bus-conflict detection

Test Pattern Generation (TPG) for sequential and/or 3-state circuits involves two important aspects which often are handled incorrectly: bus conflict detection and completeness of search in TPG. The correct handling of both aspects strongly depends on the signal model used by TPG. We propose a novel, set-based, signal model using the power-set (i.e., the set of all possible subsets) of the basic values {0, 1, Z}. TPG using this signal model guarantees complete search, provides exact bus-conflict detection, and is more efficient than TPG using the traditional signal models for J-state and sequential circuits. Experimental results demonstrate this by higher fault efficiencies combined with a large reduction of backtracking and computing time for sequential ISCAS'89 and industrial circuits.
The Role of Psychological and Physiological Factors in Decision Making under Risk and in a Dilemma

Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV), which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context.
Hot times, hot places. Youths’ risk perceptions and risk management in Chicago and Rotterdam

ABSTRACT Many young people in low-income neighbourhoods are considered to be at risk of poor social outcomes and of becoming victims of violence and crime. This exploratory study focuses on how young people perceive risk and navigate their environment in two low-income, multi-ethnic neighbourhoods, one in Rotterdam and one in Chicago. We conducted in-depth interviews and mental mapping exercises with young people aged 14–19 in both sites. We found that neighbourhoods matter because they expose young people to certain kinds of risks, but also that their responses were shaped by their perceptions and interpretations of these risks. Moreover, we illustrate the dynamic and interactive nature of these processes of risk perception and management by discussing the ways in which different groups occupy and use, or travel through, public space at different times of the day. We argue that risk in disadvantaged neighbourhoods is not a static dimension in young people’s lives but rather emerges from an ongoing and complex interaction between perception, interpretation and response that can be seen as a kind of boundary work.
The Role of Trade Associations in Market Discourse and Cognition

This dialog examines the role that trade associations play in influencing the cognitive interpretations that develop within markets. It identifies how trade associations can enable cognition by providing a space for discourse as well as influence its outcome by playing an active role in the unfolding discourse. Taking account of trade associations within can broaden our understanding of how and why cognitive interpretations form within markets.
The complementary aspect of automatically and manually generated test case sets

The test is a mandatory activity for software quality assurance. The knowledge about the software under testing is necessary to generate high-quality test cases, but to execute more than 80% of its source code is not an easy task, and demands an in-depth knowledge of the business rules it implements. In this article, we investigate the adequacy, effectiveness, and cost of manually generated test sets versus automatically generated test sets for Java programs. We observed that, in general, manual test sets determine higher statement coverage and mutation score than automatically generated test sets. But one interesting aspect recognized is that the automatically generated test sets are complementary to the manual test set. When we combined manual with automated test sets, the resultant test sets overcame in more that 10%, on average, statement coverage and mutation score when compared to the rates of manual test set, keeping a reasonable cost. Therefore, we advocate that we should concentrate the use of manually generated test sets on testing essential and critical parts of the software.
Impact of gender on in-hospital mortality of patients with acute myocardial infarction undergoing percutaneous coronary intervention: an evaluation of the TAMIS-II data.

OBJECT It is a matter of concern that women have higher in-hospital mortality rates than men with percutaneous coronary intervention (PCI), however, it is not yet clear whether significant gender differences exist. We studied the influence of gender on the characteristics and in-hospital mortality among patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS We used data from 15 acute care hospitals included in the sample from the Tokai Acute Myocardial Infarction Study II (TAMIS-II), a prospective study of all patients admitted to these hospitals from 2001 to 2003 with a diagnosis of AMI. We abstracted the baseline and procedural characteristics from detailed chart reviews which included not only physician notes but also nursing notes, and a questionnaire which included baseline characteristics, procedural course and in-hospital mortality. Multivariate analysis was performed, controlling for age and other variables which were found to be significantly different between men and women by chi-square test or unpaired t test. PATIENTS A total of 566 women and 2,048 men were included in the present study. RESULTS There were gender differences in age, comorbid conditions, smoking status, body mass index, activities of daily livings, heart failure on presentation, duration of stay, angiographic data, transfer to ICU/CCU, and thrombolytic drugs. In univariate analysis, women had a higher in-hospital mortality rate than did men; however, this gender difference disappeared after adjustment for age and other variables. CONCLUSION Our study demonstrated that women with AMI who undergo PCI do not have a higher in-hospital mortality rate than men.
Synchronizing chaotic circuits

The authors describe the conditions necessary for synchronizing a subsystem of one chaotic system with a separate chaotic system by sending a signal from the chaotic system to the subsystem. The general scheme for creating synchronizing systems is to take a nonlinear system, duplicate some subsystem of this system, and drive the duplicate and the original subsystem with signals from the unduplicated part. This is a generalization of driving or forcing a system. The process can be visualized with ordinary differential equations. The authors have build a simple circuit based on chaotic circuits described by R. W. Newcomb et al. (1983, 1986), and they use this circuit to demonstrate this chaotic synchronization. >
Well-poised hypergeometric service for diophantine problems of zeta values | NOVA. The University of Newcastle's Digital Repository

On montre comment les concepts classiques de series et integrales hypergeometriques bien equilibrees devient crucial dans l'etude des proprietes arithmetiques des valeurs de la fonction zeta de Riemann. Par ces arguments, on obtient (1) un groupe de permutations pour les formes lineaires en 1 et ζ(4) = π 4 /90 donnant une majoration conditionnelle de la mesure d'irrationalite de ζ(4); (2) une recurrence d'ordre deux pour ζ(4) semblable a celles introduites par Apery pour ζ(2) et ζ(3), ainsi que des recurrences d'ordre reduit pour les formes lineaires en des valeurs de la fonction zeta aux entiers impairs; (3) un gros groupe de permutations pour une famille d'integrales multiples generalisant les integrales dites de Beukers pour ζ(2) et ζ(3).