Miracle-dz/UniFAR-FTUs huggingface dataset:
Ingenol-3-Angelate Suppresses Growth of Melanoma Cells and Skin Tumor Development by Downregulation of NF-κB-Cox2 Signaling

Background A recent focus in skin cancer prevention intervenes though modulating molecular links between inflammation and cell growth signaling, such as NF-κB. This study elucidates the effect of a non-tumor promoting phorbol ester, ingenol-3-angelate (I3A), on the growth of human melanoma cells and on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation and 7,12-Dimethylbenz(a)anthracene (DMBA)-induced skin carcinoma in mice. Material/Methods Cell viability was assessed by MTT assay, cell proliferation by clonogenic assay, apoptosis and cell cycle arrest was analyzed by flow cytometry, protein expression was studied by IHC and Western blotting, and gene expression by qPCR. Results I3A suppressed the survival and proliferation of human melanoma cells with estimated IC50 values around 38 and 46 μM for A2058 and HT144 cell, respectively. I3A activated the protein levels of PKCδ and PKCɛ, which induced apoptosis by activating caspase-9 and caspace-3 followed by lowering of mitochondrial membrane potential and enhancing DNA fragmentation. I3A induced G1 phase cell cycle arrest as well as G2/M phase arrest in both cell lines. I3A inhibited the levels of NF-κB p65 protein as well as phosphorylation of p65 and its nuclear translocation. I3A suppressed the gene expression of NF-κB, COX-2 and iNOS. I3A inhibited TPA-induced inflammation and epidermal hyperplasia in female ICR mice by downregulating NF-κB and iNOS. I3A suppressed the growth of skin tumor in DMBA-induced mice in dose-dependent manner. Conclusions The mechanism of I3A induces apoptosis in human melanoma cells and suppresses skin inflammation and carcinoma via downregulation of NF-κB-iNOS-COX-2 signaling.
Self–employed women — new opportunities, old challenges?

In this paper it is argued that the gender of an individual entering self–employment will significantly affect the experience of owning a business. Given that women are subject to patriarchal pressures that underlie their subordination in society, it is argued that being female will affect the experience of self–employment from initiation of the firm, to development of the enterprise through to the manner of daily management challenges. This hypothesis is evaluated through a matched study of male and female small business owners where the effect of gender upon the experiences of small firm ownership is evaluated.
EPISODES OF SYSTEMIC AND BORDERLINE FINANCIAL CRISES

The following table presents information on 113 systemic banking crises (defined as much or all of bank capital being exhausted) that have occurred in 93 countries since the late 1970s. The table also provides information on 50 borderline and smaller (nonsystemic) banking crises in 44 countries during that period. Some judgment has gone into the compilation of this list, not only for countries lacking data on the size of the losses but also for countries where official estimates understate the problem. For instance, at some point in the 1990s nearly every transition economy experienced a banking crisis, but not all of these were excluded to limit the number of countries with missing information.
Can Monetary Policy Surprise the Market?

This paper extracts measures of monetary policy surprises for Australia, Canada and the United States using a latent factor framework. We distinguish monetary policy surprises which occur when central banks report new assessments of the economy (or do not reinforce changes expected by market assessments) from those when policy makers appear to change their preferences. Changing policy preferences are evident in all jurisdictions, particularly during periods of stress. No-change policy announcements have distinctly differing impacts across the three countries; in Canada these have the same impact as policy changes, in Australia they are not discernibly different to a normal trading day and the US market lies between these scenarios. The revealed differences in size and type of the policy surprise outcomes for these operationally similar central banks suggests that the role of transparency policy is more subtle than previously appreciated.
What Happened to the Three-Legged Centipede Game?

In the last two decades, several frameworks have been proposed to analyze the question of whether common knowledge of rationality is sufficient to justify the play of backward induction (BI) in games of perfect information. Three strands of literature have addressed this issue: the literature on equilibrium refinements, the literature on knowledge-based epistemology and the literature on interactive epistemology. This paper surveys seminal frameworks within the first two strands of research and assesses the extent to which they provide a satisfactory solution to the problem. These approaches are illustrated using a three-legged version of Rosenthal's centipede game, which is the classical example in the literature. The paper argues that some of these frameworks provide sensible answers to the riddle of BI or, at least, succeed in bringing the paradox to another level. The paper also points at consistency problems in the body of refinements of Nash equilibrium revealed by the surveyed literature.
Comparative Efficacy of Antiarrhythmic Agents in Preventing Halothane-Epinephrine Arrhythmias in Rats

Background:Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na+ -, K+ - and Ca2+ - channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. Methods:Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia In 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. Results:In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 ± 3.2, 11.1 ± 0.6, and 39.0 ± 3.9 µg/kg, respectively, and the corresponding plasma concentrations were 4.3 ± 0.8, 103.7 ± 9.2, and 246.7 ± 28.9 µg/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na+ - and K+ - channel blocker), E-4031(K+ - channel blocker), or amiodarone(K+ - channel blocker with Na+ -, Ca2+ -, and betablocking activity) increased significantly, i.e., 4.2,4.2,5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 µg/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias Induced by epinephrine, 16 µg/kg intravenously (P < 0.01). Conclusions:It was concluded that agents with K+ - channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.
Sufficient Statistic or Not? The Elasticity of Taxable Income in the Presence of Deduction Possibilities

The elasticity of taxable income (ETI) is often interpreted as a sufficient statistic to assess the welfare costs of taxation. Building on the conceptual framework of Chetty (2009), we show that this assertion does no longer hold for tax systems with deduction possibilities if (i) deductions generate externalities and (ii) deductions are responsive to tax rate changes. While the first condition should arguably hold for almost any imaginable tax deduction, we provide a thorough empirical examination of the second condition. Relying on rich German panel data from administrative tax records, we exploit several tax reforms that were implemented in Germany between 2001 and 2008. Our baseline estimates indicate an overall ETI of 0.49 and an elasticity of deductions with respect to the net-of-tax rate of -2.80. Given that the majority of deductions in the German income tax system generate externalities, our nonzero deduction elasticity suggests that the ETI is not sufficient to calculate the welfare cost of taxation.
Patenting as a competitive tactic in multipoint competition

Purpose – The paper's aim is to build a model that predicts the optimum tactics for capitalizing on inventions within the context of competitive interaction among large firms. For patenting, the paper seeks to show how invention value and firm rivalry drive the tactics of competing, deterring competitors, retreating from markets, and cooperating. It also aims to explore the effects of the contingencies of patent bulking, technology complexity, spheres of influence, resource similarity, and complementary‐resource tacitness.Design/methodology/approach – The work is conceptual.Findings – The base model shows that patenting can be used to protect markets where there is high invention‐value and high rivalry. When both invention‐value and rivalry are low, the best tactic is to cooperate. When value is high and rivalry low, patenting can be used as a signaling and deterring mechanism, but when value is low and rivalry is high the best option is to let patents lapse and retreat from markets. The moderating effect.
Risk Aversion and Information Structure: An Experimental Study of Price Variability in the Securities Markets

This study investigates the differences in the behaviors between the speculative investors and the conservative investors in two separate experimental markets. Although the market for speculators shows greater price volatility in both bid/ask spread within a trade as well as with intraperiod variances, it exhibits several desirable properties. Specifically, the price patterns tend to converge closer, and at a greater speed to either the prior information equilibrium price or the rational expectation equilibrium price. It also achieves better allocational efficiency. And, it is also less likely to be misled by potentially "false" price information.
Extraintestinal nematodes of the red fox Vulpes vulpes in north-west Italy

Abstract Extraintestinal nematodes of the red fox (Vulpes vulpes) are a wide group of parasites that infect wild and domestic carnivores and occasionally humans. Nematodes in the cardiopulmonary system, stomach, urinary apparatus and muscle tissue of 165 red foxes (Vulpes vulpes) from north-west Italy (Liguria and Piedmont) were investigated between 2009 and 2012. Of the cardiopulmonary nematodes, a high prevalence of Angiostrongylus vasorum and Eucoleus aerophilus (syn. Capillaria aerophila) was found, 78.2% and 41.8% respectively; Crenosoma vulpis (15.8%) and Filaroides spp. (4.8%) were also found. Spirocerca lupi (23.5%), Aonchotheca putorii (syn. Capillaria putorii) (8.6%) and Physaloptera spp. (2.5%) were detected in the stomach and Pearsonema plica (syn. Capillaria plica) (56.8%) in the bladder. Eucoleus boehmi (syn. Capillaria boehmi) was also detected in the nasal cavities of one of the two foxes examined. A coprological examination revealed eggs of E. aerophilus, A. putorii, S. lupi, Physaloptera spp. and eggs of intestinal parasites. Filarial worms were absent in all the 165 animals examined, nor was there evidence of Trichinella spp. in any of the foxes. The foxes were found to host a high prevalence of many species of extraintestinal nematodes. The prevalence of A. vasorum in foxes found in the present study is among the highest in Europe. In addition, to the best of our knowledge, E. boehmi and Filaroides spp. have never been reported before in this host in Italy.
Broiler production in Flanders, Belgium: current situation and producers' opinions about animal welfare

The aim of this paper is to provide up-to-date information about the status of broiler production in Flanders (the northern region of Belgium) and the opinion of Flemish broiler producers on animal welfare. Our review revealed that intensification of Flemish broiler production has continued, as characterised by a decreasing number of production plants with up-scaled production. Results of a quantitative survey of Flemish broiler producers showed that the typical broiler house is 21 years old and houses 35,000 mixed-sex Ross broilers indoors on wood shavings or straw. The commonly-used modal management implies thinning one-fifth of the flock at the age of 35 days. The remaining broilers are slaughtered when they are 42 days old and weigh an average of 2.4 kg. The median unassisted mortality rate is 2% and another 0.5% are culled. Further scaling-up of production units is not viewed favourably by producers, particularly as related to consumer acceptance. Producers state they place great importance on animal welfare and do not agree that broiler welfare is poor. A small minority of producers plan to invest in improving broiler welfare in the near future. They see few advantages in paying more attention to broiler welfare or providing outdoor access to improve their public image and consumer acceptance. Producers define animal welfare mainly in terms of good health, feeding and housing and consider aspects that relate to the birds' ability to express appropriate behaviour as less important. We discuss how this concept of ‘animal welfare’ corresponds to that reported by other people with farming backgrounds. Unfortunately this belief contradicts the perception of citizens and consumers and the assumptions underlying the proposed European standards for monitoring farm animal welfare as developed by the Welfare Quality® consortium.
A cross‐cultural study of screen‐tourists' profiles

Purpose – The purpose of this paper is a cross‐cultural analysis to compare the profiles of international screen‐tourists by nationalities. Also it investigates the screen‐tourism concept as associated with the Hallyu phenomenon. Owing to the nature of the topic being examined, an instrument with study‐specific items was created.Design/methodology/approach – The objectives of this paper were achieved through the critical review of previous screen‐tourism literature combined with a structured on‐site survey which included both open‐ and close‐ended questions with inbound tourists who were visiting the Daejanggeum Theme Park in South Korea.Findings – The principal value of this study can be seen in its offering of a general overview of the characteristics of screen‐tourists induced by the television drama Daejanggeum. The outcomes of this study concurred with the findings of some previous research which indicated the powerful impact of consuming popular media products including television dramas on destinat.
International river basin organizations: variation, options and insights

Permanent international river basin organizations (IRBOs) come in many shapes and sizes, ranging from those which are mainly facilitative in nature to those empowered to act on their own. Although differences in IRBO types may have important impacts on transboundary water resources management, systematic analysis of variation in their structure and responsibilities is scant. This paper synthesizes and applies a typology to determine the structural composition, abundance, spatial distribution, scale and in-basin configurations of the different forms of IRBOs. The results provide a set of options for future IRBOs, and serve to ground-truth and nuance theoretical divisions between different types of organizations in transboundary basins.
Interleukin-8 Expression Is Regulated by Histone Deacetylases through the Nuclear Factor-κB Pathway in Breast Cancer

We have reported recently that the chemokine interleukin 8 (IL-8)/CXCL8 was overexpressed in invasive estrogen receptor (ERα)-negative breast cancer cells compared with ERα-positive breast cancer cells. We now demonstrate that histone deacetylases (HDACs) play an essential role in the regulation of IL-8 gene expression in ERα-positive MCF-7 breast cancer cells. Treatment of MCF-7 cells with the HDAC inhibitor trichostatin A (TSA) led to a strong up-regulation of IL-8 protein and RNA levels in MCF-7 cells. The up-regulation of IL-8 in MCF-7 cells was time- and concentration-dependent. Moreover, run-on and transfection experiments demonstrated that IL-8 induction by HDAC inhibitors was transcriptional and involved mainly the nuclear factor-κB (NF-κB) site of the IL-8 promoter. These observations are corroborated by an up-regulation of NF-κB activity in MCF-7 cells in the presence of TSA. In addition, blocking NF-κB pathway by adenoviral delivery of a dominant-negative IκBorIκB kinase complex 2 (IKK2) mutant abolished IL-8 gene induction by histone deacetylase inhibitors. HDAC inhibitors triggered IKK phosphorylation and up-regulated p65 nuclear translocation, although they decreased the protein levels of IκBα, which accounts for NF-κB activation. TSA increased binding of acetylated histone 3 to the IL-8 gene promoter. In summary, our results demonstrate that NF-κB pathway repression by HDAC is responsible for the low expression of IL-8 in ERα-positive breast cancer cells.
Dual Allegiance and Knowledge Sharing in Open Source Software Firms

Employees of commercial software firms who participate in open source software projects are found to be allegiant to both their company and the open source community. In this paper we examine how these employees' dual allegiance influences their knowledge sharing behaviour. We adopt Husted and Michailova's model on dual allegiance and knowledge sharing in inter-firm R&D collaborations to the context of open source software firms. We argue that the type of allegiance the individual holds towards their employing firm and the open source community has a strong influence of how they share knowledge with other community members. We use the examples of two open source software firms in New Zealand to ground the empirical inspiration of our paper and to illustrate our key ideas and arguments. We discuss the knowledge governance challenges imposed by employees' dual allegiance and how managers of open source software firms can balance the demands of the open source community and the interests of the clients.
Sustainability of a Pay‐As‐You‐Go Pension System in a Small Open Economy with Ageing, Human Capital and Endogenous Fertility

The aim of the article is to theoretically investigate if a pay-as-you-go (PAYG) pension system is sustainable in the presence of a declining population and increasing longevity of the retired generation. For this purpose, we use an overlapping generation model with endogenous fertility, endogenous longevity and human capital accumulation in a small open economy. We find that pensions will always increase as long as it is beneficial for parents to invest in human capital. Furthermore, we get the result that the ratio between pension benefits and the consumption of the young generation will strive to a positive limit value, and that a pure PAYG pension system will not run into any solvency problem due to a decreasing fertility rate or ageing.
Gcn5p Plays an Important Role in Centromere Kinetochore Function in Budding Yeast

ABSTRACT We report that the histone acetyltransferase Gcn5p is involved in cell cycle progression, whereas its absence induces several mitotic defects, including inefficient nuclear division, chromosome loss, delayed G2 progression, and spindle elongation. The fidelity of chromosome segregation is finely regulated by the close interplay between the centromere and the kinetochore, a protein complex hierarchically assembled in the centromeric DNA region, while disruption of GCN5 in mutants of inner components results in sick phenotype. These synthetic interactions involving the ADA complex lay the genetic basis for the critical role of Gcn5p in kinetochore assembly and function. We found that Gcn5p is, in fact, physically linked to the centromere, where it affects the structure of the variant centromeric nucleosome. Our findings offer a key insight into a Gcn5p-dependent epigenetic regulation at centromere/kinetochore in mitosis.
Preferences for skewness: evidence from a binary choice experiment

In this paper, we experimentally test skewness preferences at the individual level. Several prospects that can be ordered with respect to the third-degree stochastic dominance criterion are ranked by the participants of the experiment. We find that the skewness of a distribution has a significant impact on the decisions. Yet, while skewness has an impact, its direction differs substantially across subjects: 39% of our subjects demonstrate a statistically significant preference for skewness and 10% seem to avoid skewness (at 5% level). On the level of individual decisions we find that the variances of the prospects and subjects’ experience increase the probability of choosing the lottery with greater skewness.
Melatonin potentiates glycine currents through a PLC/PKC signalling pathway in rat retinal ganglion cells

In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin‐induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT2 receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT2 receptor antagonist 4‐P‐PDOT. The melatonin effect was blocked by intracellular dialysis of GDP‐β‐S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)‐specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)‐PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin‐induced potentiation. The melatonin effect persisted when [Ca2+]i was chelated by BAPTA, and melatonin induced no increase in [Ca2+]i. Neither cAMP‐PKA nor cGMP‐PKG signalling pathways seemed to be involved because 8‐Br‐cAMP or 8‐Br‐cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H‐89 and the PKG inhibitor KT5823 did not block the melatonin‐induced potentiation. In consequence, a distinct PC‐PLC/PKC signalling pathway, following the activation of Gi/o‐coupled MT2 receptors, is most likely responsible for the melatonin‐induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light‐evoked glycine receptor‐mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner retina.
Vasoactive intestinal peptide and inflammatory cytokines enhance vascular endothelial growth factor production from epidermal keratinocytes

Background Overexpression of vascular endothelial growth factor (VEGF) in epidermal lesions of psoriasis is well documented; however, its underlying mechanisms are largely unknown. We have recently demonstrated that vasoactive intestinal peptide (VIP) induces the production of cytokines such as interleukin‐6 and stem cell factor from keratinocytes, thereby contributing to the development of inflammatory dermatoses such as psoriasis.