Manipulating Scrip Systems: Sybils and Collusion

Game-theoretic analyses of distributed and peer-to-peer systems typically use the Nash equilibrium solution concept, but this explicitly excludes the possibility of strategic behavior involving more than one agent. We examine the effects of two types of strategic behavior involving more than one agent, sybils and collusion, in the context of scrip systems where agents provide each other with service in exchange for scrip. Sybils make an agent more likely to be chosen to provide service, which generally makes it harder for agents without sybils to earn money and decreases social welfare. Surprisingly, in certain circumstances it is possible for sybils to make all agents better off. While collusion is generally bad, in the context of scrip systems it actually tends to make all agents better off, not merely those who collude. These results also provide insight into the effects of allowing agents to advertise and loan money. While many extensions of Nash equilibrium have been proposed that address collusion and other issues relevant to distributed and peer-to-peer systems, our results show that none of them adequately address the issues raised by sybils and collusion in scrip systems.Comment: 20 pages, 5 figures. To appear in the Proceedings of The First Conference on Auctions, Market Mechanisms and Their Applications (AMMA '09

In vitro screening of embryos by whole-genome sequencing: now, in the future or never?

What are the analytical and clinical validity and the clinical utility of in vitro screening of embryos by whole-genome sequencing? At present there are still many limitations in terms of analytical and clinical validity and utility and many ethical questions remain. Whole-genome sequencing of IVF/ICSI embryos is technically possible. Many loss-of-function mutations exist in the general population without serious effects on the phenotype of the individual. Moreover, annotations of genes and the reference genome are still not 100 correct. We used publicly available samples from the 1000 Genomes project and Complete Genomics, together with 42 samples from in-house research samples of parents from trios to investigate the presence of loss-of-function mutations in healthy individuals. In the samples, we looked for mutations in genes that are associated with a selection of severe Mendelian disorders with a known molecular basis. We looked for mutations predicted to be damaging by PolyPhen and SIFT and for mutations annotated as disease causing in Human Genome Mutation Database (HGMD). More than 40 of individuals who can be considered healthy have mutations that are predicted to be damaging in genes associated with severe Mendelian disorders or are annotated as disease causing. The analysis relies on current knowledge and databases are continuously updated to reflect our increasing knowledge about the genome. In the process of our analysis several updates were already made. At this moment it is not advisable to use whole-genome sequencing as a tool to set up health profiles to select embryos for transfer. We also raise some ethical questions that have to be addressed before this technology can be used for embryo selection. This research was supported by: Research Council KU Leuven (Projects: GOA/10/09 MaNet, KUL PFV/10/016 SymBioSys); Flemish Government: IWT Agency for Innovation by Science and Technology (Project: OO ExaScience Life), Hercules Foundation (Project: Hercules III PacBio RS), iMinds Future Health Department (Projects: SBO 2013, ArtD Instance), Flemish tier-1 Supercomputer (Project: VSC Tier 1 Exome sequencing); K.H. was supported by the Centre for Society and Life Sciences (CSG, non-profit organization) (Project number: 70.1.074). None of the authors has any conflict of interest to declare. N/A

Unraveling the behavior of oral drug products inside the human gastrointestinal tract using the aspiration technique: History, methodology and applications

Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, frequently applied in the non-clinical stage of drug product development. Sampling techniques are presently not only being considered as a stand-alone technique but are also used in combination with other in vivo techniques (e.g., gastric motility recording, magnetic resonance imaging (MRI)). By doing so, various physiological variables can be mapped simultaneously and evaluated for their impact on luminal drug and formulation behavior. This comprehensive review aims to describe the history, challenges and opportunities of the aspiration technique with a specific focus on how this technique can unravel the luminal behavior of drug products inside the human GI tract by providing a summary of studies performed over the last 20 years. A section ‘Best practices’ on how to perform the studies and how to treat the aspirated samples is described. In the conclusion, we focus on future perspectives concerning this technique. © 2020 The Author(s

Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene

Contains fulltext : 215284.pdf (publisher's version ) (Open Access)Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 x 10(-7)). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology

Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis

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