Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Analysis of Leukocyte Type-I Interferon Production and Risk of Coronary Artery Disease

Objective—Patients with systemic lupus erythematosus are genetically predisposed to enhanced production of the type-I interferon IFN-&agr; and are also at elevated risk of developing atherosclerosis compared with healthy subjects. We aimed to test whether genetic predisposition to increased type-I IFN production affects risk of coronary artery disease. Approach and Results—Using a list of 11 single nucleotide polymorphisms from the results of genome-wide association studies for systemic lupus erythematosus, which we hypothesised would be enriched in variants that regulate type-I IFN production, we identified a genetic risk score based on 3 single nucleotide polymorphisms (rs10516487, rs3131379 and rs7574865), which correlated significantly with production of IFN-&agr; by human peripheral leukocytes stimulated with CpG-oligonucleotide (n=60, P=1.50×10−5). These single nucleotide polymorphisms explained 27.8% of variation in the CpG-oligonucleotide-induced IFN-&agr; response and were also associated with Toll-like receptor-7/8– and Toll-like receptor-9–dependent IFN-&agr; and IFN-&bgr; responses, but were not associated with inflammatory cytokine production in response to Toll-like receptor-4 stimulation or risk of coronary artery disease in 22 233 cases and 64 762 controls (odds ratio 1.00, 95% CI 0.98–1.02) using Mendelian randomization–based analyses. Coronary artery disease risk was also not associated with the full panel of 11 systemic lupus erythematosus single nucleotide polymorphisms or loci responsible for the monogenic type-I interferonopathies Aicardi-Goutières syndrome and Spondyloenchondrodysplasia with immune dysregulation. Conclusions—The results argue against the potential utility of drugs targeting type-I IFN production for coronary artery disease. The use of genetic variants that modify leukocyte signaling pathways, rather than circulating biomarkers, as instruments in Mendelian randomization analyses may be useful for studies investigating causality of other candidate pathways of atherogenesis.
Mortgage Origination and the Rise of Securitization: An Incomplete-Contracts Model

Recent empirical studies find that securitised mortgages yield higher default rates than those which are originated and held by the same party, raising a number of theoretical puzzles which we address with a model based on incomplete contracts. Our model that combines the features of diversion (along the lines of Hart and Moore 1989, 1998), with asymmetric information regarding borrowers default risk (as in Stiglitz and Weiss 1981) and soft-information screening by lenders. We show that securitisation weakens the incentive to screen compared with bank originated-and-held-loans, and that securitisation is more prevalent (inter-alia) with rising house prices, lower interest rates, reduced liquidation costs and higher bank regulation costs. Extending our basic model to the case of stochastic prices allows us to analyse strategic default: Enforcement of recourse loans or policies to encourage renegotiation reduces repayments and default rates in our model. In a final extension, we assume a rise in the volume of mortgage-default properties raises the depreciation rate of such properties in the second-hand market. This systemic factor introduces multiple equilibria, i.e. either securitised or bank-held mortgages (not both at the same time) exist within a region. Securitised mortgages can generate significantly lower welfare if depreciation is sufficiently high so that mortgage markets in this region are fragile if external factors can shift the equilibrium from banking (with its low default rate) to securitisation (with its higher rate).
Comparison of enzyme-linked immunosorbent assay with enzyme-linked fluorescence assay with automated readers for detection of rubella virus antibody and herpes simplex virus

The enzyme-linked immunosorbent assay (ELISA) was compared with the enzyme-linked fluorescence assay (ELFA) for the detection of rubella antibody and herpes simplex virus antigen. Test parameters, specimens, antigen or antibody, and conjugates for the two types of assays were identical except that p-nitrophenyl phosphate was used as the substrate for the ELISA and 4-methylumbelliferyl phosphate was used as the substrate for ELFA. Automated readers were used for both assays. Antibody titers and sensitivity of antigen detection were quite similar for ELISA and ELFA. ELFA for rubella antibody, however, could be conducted with less antigen or shorter substrate incubation time (5 min for ELFA versus 30 min for ELISA). For herpes simplex virus antigen detection, ELFA could also be read after a shorter substrate incubation time (15 min for ELFA versus 30 min for ELISA). Clear polystyrene microtiter plates routinely used for ELISA could be used for ELFA, but clear polyvinyl chloride plates had high background fluorescence. Black polystyrene and polyvinyl chloride plates gave lower background fluorescence than did clear plates. ELFA is of particular value as a substitute for ELISAs in which long substrate incubations are required or antigens of only low titer are available.
A Genetic Map of the Modern Urban Society of Amsterdam

Genetic differences between individuals underlie susceptibility to many diseases. Genome-wide association studies (GWAS) have discovered many susceptibility genes but were often limited to cohorts of predominantly European ancestry. Genetic diversity between individuals due to different ancestries and evolutionary histories shows that this approach has limitations. In order to gain a better understanding of the associated genetic variation, we need a more global genomics approach including a greater diversity. Here, we introduce the Healthy Life in an Urban Setting (HELIUS) cohort. The HELIUS cohort consists of participants living in Amsterdam, with a level of diversity that reflects the Dutch colonial and recent migration past. The current study includes 10,283 participants with genetic data available from seven groups of inhabitants, namely, Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, Ghanaian, and Javanese Surinamese. First, we describe the genetic variation and admixture within the HELIUS cohort. Second, we show the challenges during imputation when having a genetically diverse cohort. Third, we conduct a body mass index (BMI) and height GWAS where we investigate the effects of a joint analysis of the entire cohort and a meta-analysis approach for the different subgroups. Finally, we construct polygenic scores for BMI and height and compare their predictive power across the different ethnic groups. Overall, we give a comprehensive overview of a genetically diverse cohort from Amsterdam. Our study emphasizes the importance of a less biased and more realistic representation of urban populations for mapping genetic associations with complex traits and disease risk for all.
Pheochromocytoma as the first manifestation of von Hippel-Lindau disease.

BACKGROUND von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma. METHODS We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease. RESULTS The mean age at pheochromocytoma diagnosis was 29 +/- 14 years (5 to 62 years). Bilateral tumors were documented in 15 (42%) cases, paraganglioma was associated with adrenal pheochromocytoma in four cases, and malignant pheochromocytoma occurred in three cases. Prevalence of pheochromocytoma revealing von Hippel-Lindau disease was 20 (53%) out of 36. In six cases pheochromocytoma was the only manifestation of the disease. CONCLUSIONS In the interest of the patients themselves and of family members who are at risk, search for von Hippel-Lindau disease must be systematic in the presence of pheochromocytoma. Basic checkup may be completed with familial inquiry, ophthalmoscopy, cerebral magnetic resonance imaging, abdominal ultrasonography, and computed tomography-scan for detection of latent lesions. In the future, after characterization of von Hippel-Lindau disease gene mutations, molecular diagnosis is going to be possible in individual patients.
JNK supports survival in melanoma cells by controlling cell cycle arrest and apoptosis

JNK1/2 proteins belong to the family of stress‐activated protein kinases. They play a complex role in growth regulation, inducing either cell death or growth support. In this report, we provide evidence that, in human melanoma cells, JNK inhibition with the small molecule inhibitor SP600125 induces either predominantly a G2/M arrest or apoptosis depending on the cell line. In 1205Lu cells, JNK inhibition induced cell cycle arrest through p53‐dependent induction of p21Cip1/Waf1 expression, while in WM983B cells, induction of apoptosis by JNK inhibition was accompanied by p53, Bad and Bax induction, not p21Cip1/Waf1. JNK inhibition with the small molecule inhibitor SP600125 slowed growth of all cell lines, although the effect was markedly greater in cells exhibiting high phospho‐ (P‐)JNK1 levels. Specific gene knockdown of JNK1 by means of siRNA oligonucleotides inhibited cell growth only in melanoma cell lines exhibiting high P‐JNK1 levels. siRNAs directed against JNK2 did not reduce cell growth in any of the cell lines tested. Together, our findings demonstrate that JNK, and in particular the JNK1 isoform, support the growth of melanoma cells, by controlling either cell cycle progression or apoptosis depending on the cellular context.
Comparison of Accelerated Corneal Collagen Cross-linking Types for Treating Keratoconus

ABSTRACT Purpose: To compare the results of different protocols for accelerated corneal collagen cross-linking (CXL) in patients with progressive keratoconus. Materials and method: This prospective comparative study involved 40 patients treated with intended UV-A radiance of 5.4 J/cm2 in 74 eyes (Group 1) and 42 patients treated with radiance of 7.2 J/cm2 in 72 eyes (Group 2). Visual acuity, subjective manifest refraction and corneal topography were analyzed before and 12 months after surgery in both groups. Postoperative complications were also noted. The results of the two protocols were statistically compared. Results: There were no statistically significant differences between the groups in uncorrected distance visual acuity, corrected distance visual acuity or corneal topography pre- or postoperatively. The differences in keratometric readings (K apex, SimK1 and SimK2) and refractive results were not significant. Conclusion: The application of total intended UV-A radiance of 5.4 J/cm2 or 7.2 J/cm2 for accelerated CXL in patients with progressive keratoconus resulted in similar refractive and topographic outcomes.
An Introduction to Stress Testing and Risk Integration in Banks Academic Press (an Imprint of Elsevier)

Since the 2007-09 crisis, increasing attention has been devoted to capital adequacy and balance sheet integrity. Banks have been required to improve the quality of their own funds, strengthen their liquidity structure, and enforce their risk management processes. This paper serves the purpose of introducing the book Stress testing and risk integration in banks. The latter outlines the regulatory response to the recent financial crunch. On this subject, stress tests and risk integration are useful tools to enhance bank resilience against adverse conditions. The illustrative example of Bank Alpha points out how an international bank runs its business. It is used throughout the book to point out all complex challenges one needs to face when modelling risks. As in an executive summary, this introduction highlights some of Bank Alphas main stress testing and risk integration results. Finally, a practical guide to explore the text is provided. It serves as a map for the reader looking for orientation during the deep-dive journey.
Investigating the Role of the Host Multidrug Resistance Associated Protein Transporter Family in Burkholderia cepacia Complex Pathogenicity Using a Caenorhabditis elegans Infection Model

This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were divided in 4 distinct groups. Only the Cystic Fibrosis isolated strains possessed profound nematode killing ability to accumulate in worms’ intestines. For the transporter analysis a complete set of isogenic nematode single Multidrug Resistance associated Protein (MRP) efflux mutants and a number of efflux inhibitors were interrogated in the host toxicity assays. The Bcc pathogenicity profile of the 7 isogenic C. elegans MRP knock-out strains functionality was classified in two distinct groups. Disabling host transporters enhanced nematode mortality more than 50% in 5 out of 7 mutants when compared to wild type. In particular mrp-2 was the most susceptible phenotype with increased mortality for 13 out 18 Bcc strains, whereas mrp-3 and mrp-4 knock-outs had lower mortality rates, suggesting a different role in toxin-substrate recognition. The use of MRP efflux inhibitors in the assays resulted in substantially increased (>40% on average) mortality of wild-type worms.
Fetal echocardiographic screening in twins for congenital heart diseases.

BACKGROUND Congenital heart disease (CHD) is the most common congenital disorder at birth. Yagel and colleagues's method of heart examination has been proved valuable in finding CHD prenatally in single pregnancies. The aim of this study was to analyze the frequency of CHD in twin pregnancies and the sensitivity of the method. METHODS A total of 1103 pregnant women with twins were enrolled in this study, including 127 cases with high-risk for CHD. Five transverse ultrasound measurements were used for fetal heart examination, including the upper abdomen view, four-chamber view, five-chamber view, pulmonary artery bifurcation view, and three-vessel view. In the fetuses who were diagnosed with CHD and whose parents requested termination of the pregnancy, autopsy of the fetal heart was performed after an abortion, and a blood sample was collected from the heart for chromosome evaluation. In the other fetuses, a close follow-up was conducted by echocardiography within one year after birth. RESULTS Antenatally, CHD was found in 12 twins, of which 4 were from the high-risk group (3.15%), and 8 from the low-risk group (0.82%). In 2 pairs of the twins, the two fetuses had a same kind of CHD (one pair had tetralogy of Fallot (TOF), another pair had rhabdomyoma). Another pair had different types of anomaly (one fetus had TOF, and the other duodenal atresia with a normal heart). Termination of pregnancy was performed in these three pairs and the autopsy of the fetal heart confirmed the ultrasound findings. In the other 9 pairs, CHD was detected in one fetus, and a normal heart in the others. In the cases who received chromosome evaluation, 2 had abnormal chromosomes. During the follow-up after birth, heart examinations confirmed the prenatal diagnosis in 7 of the 9. The diagnosis of CHD was missed antenatally in 2 pairs of twins. In both the cases, one fetus was normal, and the other was confirmed as having CHD after birth (small ventricle septum defect in one, and persistent open ductus arteriosus in the other). Thus, the total frequency of CHD was 16 (7.3/1000), which was similar to that in single pregnancies. The sensitivity of fetal echocardiography was 87.5% and the specificity was 100%. CONCLUSIONS The frequency of CHD is the same in twin as in single pregnancies. Systemic ultrasound scanning with five transverse views is effective in diagnosing fetal CHD in twin pregnancies.
Eliciting Stock Market Expectations: The Effects of Question Wording on Survey Experience and Response Validity

ABSTRACT Expectations about stock market movements are an important factor in models of investments and savings. To better understand consumers' financial behavior, economic surveys such as the Health and Retirement Study (HRS) ask participants to report expectations about the stock market. However, readability statistics suggest that the HRS' stock market expectations questions use relatively complex wording, which may contribute to their relatively high rates of missing responses. Here, the authors build on survey design research to improve the readability of these questions. In 2 experiments using national online panels, they test whether revising stock market expectation questions to reduce their difficulty affects respondents' (1) survey experience, as measured by percent of missing answers and ratings of question clarity and difficulty, and (2) response validity, as assessed by respondents' confidence in their answer and comparisons between expectations and stock market outcomes. In both studies, the authors' revisions improved survey experience. Unfortunately, revisions also decreased the perceived (Study 1) and actual (Study 2) validity of responses. The authors discuss implications of question revisions for the design of economic surveys.
Displaced Relative Changes in Historical Simulation: Application to Risk Measures of Interest Rates with Phases of Negative Rates

In this paper we introduce the displaced historical simulation model which is designed to handle negative and close-to-zero risk factors. This is an issue of recent and major interest to the financial sector, both from a regulatory and financial institutions perspective, especially in light of observed negative values for major bond yield and interest rate spread time series. In historical simulation a common approach is to consider log returns (that is, relative changes), given that the risk factors remain positive. If a risk factor allows for negative values, log returns cannot be applied and one either ignores such scenarios or switches to considering absolute changes. The latter approach implies an abrupt model change. Our displaced historical simulation model strongly improves the historical simulation by “displacing” the shifts such that negative values can be handled, smoothly moving to the limit case of using absolute shifts instead of relative shifts of the original data. Our empirical results show that compared to other models presented in the literature, models equipped with our proposed displacement feature handle situations of close-to-zero or negative risk variables particularly well.
Wearable Device-Based System to Monitor a Driver’s Stress, Fatigue, and Drowsiness

This paper proposes a wearable device-based system to monitor the abnormal conditions of a driver, including stress, fatigue, and drowsiness. The system measures the motional and physiological information of the driver using the developed wearable device on the wrist. Preprocessing is used to distinguish the valid signal parts of the measured signals, because various noises can occur in wearable sensors. Features are extracted from the signal parts, and an optimal feature set is determined by an analysis of variance and a sequential floating forward selection algorithm. To classify the driver’s state, a support vector machine-based classification method is used to obtain high generalization performance considering interdriver variance. Experiments were conducted on an indoor driving simulator, with 28 subjects, to gather data for each state. The classification accuracy was 98.43% for fivefold cross validation on the data. In a subject-independent test, the accuracy was 68.31% for the four states and 84.46% for the three states consisting of normal, stressed, and fatigued or drowsy states. Using the proposed system, the abnormal conditions of the driver can be detected and distinguished. This advantage contributes to safer and more comfortable driving. Furthermore, the utilization of the wearable device makes the system easy to use.
Assembly of Synapses: Biomimetic Assays to Control Neurexin/Neuroligin Interactions at the Neuronal Surface

The role of adhesion molecules in the assembly of synapses in the nervous system is an important issue. To characterize the role of neurexin/neuroligin adhesion complexes in synapse differentiation, various imaging assays can be performed in primary hippocampal cultures. First, to temporally control contact formation, biomimetic assays can be performed using microspheres coated with purified neurexin or with antibody clusters that aggregate neurexin. These models are combined with live fluorescence imaging to study the dynamics of accumulation of post‐synaptic components, including scaffolding molecules and glutamate receptors. To demonstrate that AMPA receptors can be recruited to nascent neurexin/neuroligin contacts through lateral diffusion, the mobility of AMPA receptors in the neuronal membrane is monitored by tracking individual quantum dots (QDs) conjugated to antibodies against AMPA receptors. Experiments monitoring the attachment and detachment of Nrx‐coated QDs to measure the rates of neurexin/neuroligin interaction can also be performed. Each of these assays is detailed in this unit. Curr. Protoc. Neurosci. 64:2.19. 1‐2.19. 30. © 2013 by John Wiley & Sons, Inc.
A new he core transmitter of a contactless power transfer system that is compatible with circular core receivers and H-shaped core receivers

Contactless power transfer systems for electric vehicles contain two types of transformers (a pair consisting of a transmitter and a receiver): a rectangular (H-shaped) core double-sided winding transformer and a circular core single-sided winding transformer. Since the magnetic field structures of these two transformers differ greatly, these two types of transformers have been incompatible in the past, although a number of compatible receivers have recently been proposed. This paper proposes a novel He core transmitter that is compatible with both types of receivers. The He core transmitter adds a central magnetic pole by dividing the winding coil of the H-shaped core transmitter. This transmitter can change the magnetic field structure by changing the connections of divided windings and can transfer power to both types of receivers. Compatibility tests at 3 kW are carried out, and the test results are presented.