Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus

INTRODUCTION: Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation. METHODS: Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed. RESULTS: Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival. CONCLUSIONS: The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease

Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery

<b>BACKGROUND AND PURPOSE</b> Anandamide and sphingosine-1-phosphate (S1P) both regulate vascular tone in a variety of vessels. This study aimed to examine the mechanisms involved in the regulation of coronary vascular tone by anandamide and S1P, and to determine whether any functional interaction occurs between these receptor systems. <br></br> <b>EXPERIMENTAL APPROACH</b> Mechanisms used by anandamide and S1P to regulate rat coronary artery (CA) reactivity were investigated using wire myography. Interactions between S1P and the cannabinoid (CB)2 receptor were determined using human embryonic kidney 293 (HEK293) cells that stably over-express recombinant CB2 receptor. <br></br> <b>KEY RESULTS</b> Anandamide and S1P induced relaxation of the rat CA. CB2 receptor antagonists attenuated anandamide-induced relaxation, while S1P-mediated relaxation was dependent on the vascular endothelium and S1P3. Anandamide treatment resulted in an increase in the phosphorylation of sphingosine kinase-1 within the CA. Conversely, anandamide-mediated relaxation was attenuated by inhibition of sphingosine kinase. Moreover, S1P3, specifically within the vascular endothelium, was required for anandamide-mediated vasorelaxation. In addition to this, S1P-mediated relaxation was also reduced by CB2 receptor antagonists and sphingosine kinase inhibition. Further evidence that S1P functionally interacts with the CB2 receptor was also observed in HEK293 cells over-expressing the CB2 receptor. <br></br> <b>CONCLUSIONS AND IMPLICATIONS</b> In the vascular endothelium of rat CA, anandamide induces relaxation via a mechanism requiring sphingosine kinase-1 and S1P/S1P3. In addition, we report that S1P may exert some of its effects via a CB2 receptor- and sphingosine kinase-dependent mechanism, where subsequently formed S1P may have privileged access to S1P3 to induce vascular relaxation

A Blockchain-Based Approach Towards Overcoming Financial Fraud in Public Sector Services

In financial markets it is common for companies and individuals to invest into foreign companies. To avoid the double taxation of investors on dividend payment - both in the country where the profit is generated as well as the country of residence - most governments have entered into bilateral double taxation treaties, whereby investors can claim a tax refund in the country where the profit is generated. Due to easily forgeable documents and insufficient international exchange of information between tax authorities, investors illegitimately apply for these tax returns causing an estimated damage of 1.8 billion USD, for example, in Denmark alone. This paper assesses the potential of a blockchain database to provide a feasible solution for overcoming this problem against the backdrop of recent advances in the public sector and the unique set of blockchain capacities. Towards this end, we develop and evaluate a blockchain-based prototype system aimed at eliminating this type of tax fraud and increasing transparency regarding the flow of dividends. While the prototype is based on the specific context of the Danish tax authority, we discuss how it can be generalized for tracking international and interorganizational transactions

MARKET ANOMALIES ON TWO-SIDED AUCTION PLATFORMS

A market anomaly (or market inefficiency) is a price distortion typically on a financial market that seems to contradict the efficient-market hypothesis. Such anomalies could be calendar, technical or fundamental related and have been shown empirically in a number of settings for financial markets. This paper extends this stream of research to two-sided auction platforms in Electronic Commerce and empirically analyzes whether calendar anomalies are persistent on such markets. Our empirical study analyzes 78,068 transactions completed between buyers and sellers on a German auction platform and covers the period between April 2005 and May 2009. We observe a persistent turn-of-the-month effect and a day-of-the-week effect that would allow buyers to realize small additional surpluses (0.3% price discount). Prices are also persistently lower in the highly competitive Christmas trade period while sellers benefit from higher prices at the beginning of every year. Overall our results support the common notion that two-sided auction platforms are rather efficient markets on which we however can observe some marginal market inefficiencies

Using Twitter to Predict the Stock Market - Where is the Mood Effect?

Behavioral finance researchers have shown that the stock market can be driven by emotions of market participants. In a number of recent studies mood levels have been extracted from Social Media applications in order to predict stock returns. The paper tries to replicate these findings by measuring the mood states on Twitter. The sample consists of roughly 100 million tweets that were published in Germany between January, 2011 and November, 2013. In a first analysis, a significant relationship between aggregate Twitter mood states and the stock market is not found. However, further analyses also consider mood contagion by integrating the number of Twitter followers into the analysis. The results show that it is necessary to take into account the spread of mood states among Internet users. Based on the results in the training period, a trading strategy for the German stock market is created. The portfolio increases by up to 36 % within a six-month period after the consideration of transaction costs

The Economic Impact of Privacy Violations and Security Breaches

Privacy and security incidents represent a serious threat for a company’s business success. While previous research in this area mainly investigated second-order effects (e.g., capital market reactions to privacy or security incidents), this study focuses on first-order effects, that is, the direct consumer reaction. In a laboratory experiment, the authors distinguish between the impact of privacy violations and security breaches on the subjects’ trust and behavior. They provide evidence for the so-called “privacy paradox” which describes that people’s intentions, with regard to privacy, differ from their actual behavior. While privacy is of prime importance for building trust, the actual behavior is affected less and customers value security higher when it comes to actual decision making. According to the results, consumers’ privacy related intention-behavior gap persists after the privacy breach occurred

Faktor - Faktor yang Berhubungan dengan Pendapatan Pedagang Kaki Lima di Kawasan Kampus Universitas Andalas

Penelitian bertujuan untuk mengetahui faktor faktor yang berhubungan terhadap pendapatan pedagang kaki lima di kawasan Universitas Andalas. Variabel yang diteliti adalah Modal (X1), lama usaha (X2), jam kerja (X3), tingkat pendidikan (X4) dan biaya (X5) serta dengan variabel Pendapatan (Y). Metode penelitian ini menggunakan Cross-tabb dengan uji chi-square. Pada penelitian ini meneliti populasi sebanyak 34 pedagang kaki lima yang terdata oleh Universitas Andalas. Hasil analisis menunjukan bahwa modal, jam kerja, dan biaya berhubungan dengan pendapatan pedagang kaki lima di kawasan Universitas Andalas. Sedangkan lama usaha dan biaya tidak tidak berhubungan dengan pendapatan pedagang kaki lima di kawasan Universitas Andalas