Miracle-dz/UniFAR-FTUs huggingface dataset:
European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

A minimum of two positive, adequate, and well‐controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case‐by‐case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases.
The Firm as an Enterprise Entity and the Tax Avoidance Conundrum: Perspectives from Accounting Theory and Policy

Abstract Notwithstanding its political dimension, international tax avoidance is also the result of a regulatory process that makes reference to overarching concepts and representations. The current debate is featured by two overarching principles of ‘negative’ and ‘positive’ taxation under the law: the one arguing for the right to minimise the tax payment, the other one for the duty to pay a fair tax amount. This debate is further featured by two distinctive approaches to tax base determination: the market basis coupled with the legal person basis, and the economic substance basis. The economic substance approach argues that the received approach grapples with economic reality featured by integrated transnational corporate groups. These groups operate across jurisdictions and have the capacity to reshape their legal-economic structuring to obtain specific tax results. An adequate response urges then to consider these groups through consolidated report (unitary approach), allocating their consolidated result to involved jurisdictions through formulary apportionment. This unitary approach is upheld by recent advances by the theory of the firm as enterprise entity, which combines law and economics with accounting. The business firm is then understood as a specific economic coordination backed by its institutional structure of production, including its accounting system. This theoretical consistency is appealing and deserves further investigation, including to foster cross-fertilisation and harmonisation of financial and tax accounting systems. But it does not imply a straightforward claim to adopt current international accounting standards for tax purposes. International accounting standards-making has been formally disconnected by national jurisdictions, it currently excludes public policy concerns, and it may be substantially unable to avoid the very same ‘specifications’ on the letter of the law that have been already paving the way to loopholes and structuring opportunities in tax regulation.
Premature fetal tissues are possible source of valuable mesenchymal stem cells.

OBJECTIVES Comparison of the ability to inhibit alloactivated lymphocytes proliferation of human Wharton Jelly (WJ) and amniotic membrane (AM) mesenchymal stem cells (MSCs) from preterm and term pregnancies. MATERIAL AND METHODS Term-WJ-MSCs (n = 5) and Preterm-WJ-MSCs (n = 1) were obtained from tissue explants by adherent method. Term-AM-MSCs (n = 5) and Preterm-AM-MSCs (n = 1) were obtained by tripsin and collagenase digestion method. Term and Preterm MSCs phenotype was confirmed in vitro by flow cytometry. To evaluate the potential of fetal and adult MSCs to diminish immunological response mixed lymphocytes reaction (MLR) has been performed. RESULTS Term and Preterm cells were positively identified as MSCs by the expression of CD73 and CD90 and CD105 with simultaneous absence of CD11b, CD14, CD19, CD34, CD45 and HLA-DR. The mean inhibition of allostimulated lymphocytes after addition of fetal derived MSCs amounted 64.8% for term AM-MSCs and 42.1% for term WJ-MSCs (for both populations the effect was statistically significant, p < 0.01). The addition of preterm-MSCs to MLR resulted in reduction of stimulated lymphocytes proliferation by 64.9% for AM-MSCs and 86.1% for WJ-MSCs. CONCLUSIONS Presented results suggest that preterm fetal tissues contain MSCs which posses similar immunosuppressive capacity as those from term pregnancies. In the future MSCs from the umbilical cord and amnion can be potentially used to prevent immuno-dependent injuries in premature newborns.
What Chinese Workers Value: An Analysis of Job Satisfaction, Job Expectations, and Labor Turnover in China

This study uses data from the 2012 China Labor Force Dynamics Survey and 2010–2012 China Family Panel Studies to investigate job satisfaction and job expectations, as well as the association between job satisfaction and job turnover by gender among employees aged 16–65. We find not only that job satisfaction levels are relatively low, with only 46% of workers explicitly satisfied, but also that worker expectations differ significantly from what their jobs actually provide. In particular, many jobs are less interesting than expected, which prevents workers from realizing their perceived potential. This expectation gap is thus a strong determinant of job satisfaction. Men and women have similar levels of job satisfaction, yet based on observables, one would expect women's job satisfaction to be lower than it actually is, thereby lending support to the gender-job-satisfaction paradox encountered in Western studies. In contrast to Western research, we find no link between job satisfaction and job change, an observation we attribute to China's unique Confucian-based work ethic.
The cell surface expression level of the human interleukin-5 receptor alpha subunit determines the agonistic/antagonistic balance of the human interleukin-5 E13Q mutein.

The human interleukin-5 (IL-5) receptor consists of an alpha-chain that specifically binds the ligand with intermediate affinity, and a beta c-chain, that associates with the IL-5/IL-5R alpha complex, leading to a high-affinity, signal transducing receptor complex. Structure-function studies showed that modification of the putative beta c-chain binding site in IL-5 (E13Q mutein) converted the molecule into an antagonist. However, analysis of the effect of this mutant IL-5 on COS-1 cells transfected with both receptor subunits, did not show reduced interaction with the beta c subunit [Tavernier, J., Tuypens, T. , Verhee, A. , Plaetinck, G. , Devos, R. , Van der Heyden, J., Guisez, Y. & Oefner, C. (1995) Proc. Natl Acad. Sci. USA 89, 7041-7045]. To gain more insight into the mechanism of IL-5 antagonism by E13Q, we tested its biological activity on two FDC-P1 subclones that express clearly different numbers of alpha-subunits yet an almost constant number of murine beta c-subunits. Here we show that E13Q has a biological activity comparable to wild-type IL-5 only when a high number of alpha-chains is present on the cells. Confirming the critical role of the IL5R alpha cell-surface expression level, treatment with suboptimal doses of a neutralising anti-IL-5R alpha antibody results in reduced activity of the mutant but not of wild-type IL-5.
Hippocampal volume and depression: insights from epilepsy surgery

Background: Major depression is common after epilepsy surgery. It has previously been suggested that surgical removal of limbic system structures such as the hippocampus may contribute to this comorbidity. Recent magnetic resonance imaging studies have found smaller hippocampal volumes in depressed patients in comparison with controls. Aims: The current study examined whether preoperative hippocampal volumes were associated with depression experienced after epilepsy surgery. Patients undergoing mesial (n = 26) and non-mesial (n = 16) temporal lobe resections were assessed preoperatively, and for 1 year postoperatively. Assessment included a clinical interview and the Beck Depression Inventory. Hippocampal volumes were measured on the preoperative T1-weighted magnetic resonance imaging scans of the patients and 41 neurologically normal controls. Results: A similar proportion of mesial and non-mesial temporal patients had a preoperative history of major depression. Postoperatively, 42% of mesial and 19% of non-mesial temporal patients were depressed. There was no relationship between hippocampal volume and preoperative depression in either group. Depression after surgery was associated with significantly smaller hippocampal volumes contralateral to the resection in the mesial temporal group (p = 0.005). This effect was seen in mesial temporal patients who developed de novo depression (p = 0.006). Hippocampal volume was unrelated to postoperative depression in the non-mesial group. Conclusion: This study highlights the role of neurobiological factors in the development of postoperative depression. These initial findings have implications for understanding depression following epilepsy surgery as well as the pathogenesis of depression more generally.
Determinants of corporate social responsibility reporting : evidence from an emerging economy

This paper aims to measure the extent of corporate social responsibility (CSR) and its determinates by non-financial companies listed on Abu Dhabi Securities Exchange. The study employs content analysis of the annual reports to measure the extent of CSR disclosure in Abu Dhabi Companies. In addition, the study adopts multiple regression analysis to identify factors influencing the extent of corporate social responsibility disclosure. The findings reveal that the level of CSR disclosure by companies listed on Abu Dhabi Securities Exchange is low with an average of 34 %, indicating that such disclosure is still not of a primary concern to these companies. The results also suggest that the extent of CSR disclosure is influenced by corporate size, industry and profitability. The paper is limited by the subjectivity of content analysis as well as it considers CSR disclosure for only one year. This study has public policy implications for the decision makers in the UAE as well as a number of other Arab and Middle East countries. This paper adds to the limited CSR literature in Arab and Middle East countries in general and the United Arab Emirates in particular. This paper not only examines the extent and determinants of corporate social disclosure but also attempts to theorize such disclosure.
Convolution Constraints for Broadband Antenna Arrays

Directional constraints are imposed on the weights of an antenna array to obtain solutions of some constrained beamforming problems. For broadband antenna arrays, formulation of a constrained beamforming problem typically requires presteering the array using steering delays. These delays create implementation problems and cause loss of system performance in the presence of implementation errors. This paper presents new kind of constraints referred to as convolution constraints, which are easy to implement, eliminate the need for presteering the array and can be used for broadband pattern synthesis. Examples are presented to demonstrate many applications of these constraints on an array weights.
Metabolism of α-thujone in human hepatic preparations in vitro

This study aims to characterize the metabolism of α-thujone in human liver preparations in vitro and to identify the role of cytochrome P450 (CYP) and possibly other enzymes catalyzing α-thujone biotransformations. With a liquid chromatography–mass spectrometry (LC-MS) method developed for measuring α-thujone and four potential metabolites, it was demonstrated that human liver microsomes produced two major (7- and 4-hydroxy-thujone) and two minor (2-hydroxy-thujone and carvacrol) metabolites. Glutathione and cysteine conjugates were detected in human liver homogenates, but not quantified. No glucuronide or sulphate conjugates were detected. Major hydroxylations accounted for more than 90% of the primary microsomal metabolism of α-thujone. Screening of α-thujone metabolism with CYP recombinant enzymes indicated that CYP2A6 was principally responsible for the major 7- and 4-hydroxylation reactions, although CYP3A4 and CYP2B6 participated to a lesser extent and CYP3A4 and CYP2B6 catalyzed minor 2-hydroxylation. Based on the intrinsic efficiencies of different recombinant CYP enzymes and average abundances of these enzymes in human liver microsomes, CYP2A6 was calculated to be the most active enzyme in human liver microsomes, responsible for 70–80% of the metabolism on average. Inhibition screening indicated that α-thujone inhibited both CYP2A6 and CYP2B6, with 50% inhibitory concentration values of 15.4 and 17.5 µM, respectively.
Use of a peripheral dexa measurement for osteoporosis screening.

BACKGROUND AND OBJECTIVES Osteoporosis is a substantial cause of morbidity and mortality in the United States. While screening for this disease is important, few studies have evaluated the role of an osteoporosis screening device in afamily practice setting. This study evaluated the influence of a peripheral-dexa (p-dexa) heel bone mineral density (BMD) measurement and a patient education program on changes in pharmacologic treatment for suspected osteopenia or osteoporosis by primary care physicians over a 1-year follow-up. METHODS Using a computerized database (ages 50 to 75 years), 1,927 women were identified. An invitation was mailed to register for a screening to have a p-dexa heel BMD scan done and to attend an osteoporosis prevention presentation. Medication history, age, height, weight, and risk factors for osteoporosis were collected. A follow-up chart review was carried out on women who werefound to have heel BMD T-scores of <-. 6 (suggested by the World Health Organization). Date of menopause onset, pharmacotherapy for osteoporosis, calcium, vitamin D, and physician intervention were assessed. RESULTS There were 292 women (15.2%) who self registered, obtained BMD testing, and attended an educational program. Of these women, 87 (30%) had at least one risk factor for osteoporosis, in addition to menopause. Mean BMD was . 489 +/- . 113 gm/cm2 (normal >.42 gm/cm2). A post-screening chart review was completed in 102 women (36.6%) at greatest risk for osteoporosis based on a T-score <-. 6. Following the intervention, 26 women were started on antiresorptive therapy (primarily estrogen), and three additional women had a second antiresorptive agent added to estrogen. CONCLUSIONS P-dexa heel BMD has utilityfor screening patients at riskfor osteoporosis. However, only 15% of invited women attended the screenings, and pharmacotherapy treatment did not significantly change after screening in the majority of women at riskfor osteoporosis, based on p-dexa screening.
Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab.

INTRODUCTION The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). MATERIALS AND METHODS The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62. RESULTS A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. CONCLUSIONS Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.
Corporate Social Responsibility and Governance: Information Disclosure in Multinational Corporations

Multinational corporations (MNCs) are facing increasing pressure on two fronts – the demand for more transparency and disclosure and the need to implement good corporate governance practices. This paper develops several testable hypotheses that address these issues based on agency theory and stakeholder management approach arguments. As such, the relationship between corporate social responsibility (CSR) programs and firm-level governance structures are discussed. CSR is measured using Transparency International's study on the disclosure practices of the world's largest MNCs. Links between board size, board independence, and duality are explored. The results indicate that board independence and board size are strongly and positively related to several CSR practices. In addition, extractive industries have a significant and positive impact on the level of CSR activities. Policy and managerial implications related to these findings are also discussed. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Information Shocks about Ability and the Decision to Enroll in Advanced Placement: Evidence from the PSAT

This study asks whether lack of information about ability helps explain why high-performing students from disadvantaged backgrounds tend to under-invest in their education. I examine an individualized signal of aptitude for Advanced Placement known as “AP Potential” that is provided in PSAT reports. By collecting high-frequency panel data on subjective beliefs from students in Oakland, California, I show that the “AP Potential” signal has informational value: students with the same scores and prior beliefs who receive the signal experience larger information shocks. These shocks lead students to revise their beliefs about their ability, the number of AP classes they plan to take, and the likelihood that they will attend a four-year college, consistent with a Bayesian updating model. I then exploit the deterministic relationship between test scores and the AP Potential signal in a Regression Discontinuity (RD) design and find that receiving the signal caused surveyed students at the margin to enroll in approximately one more AP class the following semester. This effect amounts to raising the number of highability students in college-level courses and reducing mismatch in course enrollments. The results suggest that providing a credible, individualized signal of ability is a cost-effective means of increasing human capital investments among disadvantaged students. ∗Correspondence should be sent to ndg2109@columbia.edu. I am especially grateful to W. Bentley Macleod for thoughtful comments and advice and to the Oakland Unified School District for providing access to its data and classrooms. I also thank seminar participants at Columbia University’s applied microeconomic theory and applied microeconomic research methods colloquia, in particular Miguel Urquiola, Douglas Almond, Bernard Salanie, PierreAndre Chiappori, Miikka Rokkanen, Valentina Duque, and Harold Stolper. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship.
Parallelization of Machine Learning Applied to Call Graphs of Binaries for Malware Detection

Malicious applications have become increasingly numerous. This demands adaptive, learning-based techniques for constructing malware detection engines, instead of the traditional manual-based strategies. Prior work in learning-based malware detection engines primarily focuses on dynamic trace analysis and byte-level n-grams. Our approach in this paper differs in that we use compiler intermediate representations, i.e., the callgraph representation of binaries. Using graph-based program representations for learning provides structure of the program, which can be used to learn more advanced patterns. We use the Shortest Path Graph Kernel (SPGK) to identify similarities between call graphs extracted from binaries. The output similarity matrix is fed into a Support Vector Machine (SVM) algorithm to construct highly-accurate models to predict whether a binary is malicious or not. However, SPGK is computationally expensive due to the size of the input graphs. Therefore, we evaluate different parallelization methods for CPUs and GPUs to speed up this kernel, allowing us to continuously construct up-to-date models in a timely manner. Our hybrid implementation, which leverages both CPU and GPU, yields the best performance, achieving up to a 14.2x improvement over our already optimized OpenMP version. We compared our generated graph-based models to previously state-of-the-art feature vector 2-gram and 3-gram models on a dataset consisting of over 22,000 binaries. We show that our classification accuracy using graphs is over 19% higher than either n-gram model and gives a false positive rate (FPR) of less than 0.1%. We are also able to consider large call graphs and dataset sizes because of the reduced execution time of our parallelized SPGK implementation.
Processing of the Tail Lysozyme (gp5) of Bacteriophage T4

ABSTRACT The processing site of gp5 has been determined to be between residues Val-390 and His-391, instead of Ser-351 and Ala-352 as previously reported (H. Kanamaru, N. C. Gassner, N. Ye, S. Takeda, and F. Arisaka, J. Bacteriol. 181:2739-2744). Moreover, the maturation of gp5 is abolished by null mutations in other hub genes, indicating that cleavage requires the interactions of several baseplate proteins.
Equity Market Globalization and Portfolio Rebalancing

This paper examines how the financial globalization affects international equity mutual funds' portfolio choices in emerging markets. By examining the monthly holdings of 155 international funds, we first show that these funds actively engage in a rebalancing strategy to maintain their risk preferences upon realization of excess return changes. We also document robust evidence that these funds' propensity of rebalancing is larger in a country whose equity market is more strongly correlated with the global market. The results help understand how the financial globalization may raise the portfolio risk of the international funds' equity holdings in emerging economies.