Genewise detection of variants in MEFV gene using nanopore sequencing

Familial Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for full-length MEFV gene mutation detection to aid in the diagnosis and screening of FMF. We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected. Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMF-associated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

Transverse sphericity of primary charged particles in minimum bias proton–proton collisions at √s = 0.9, 2.76 and 7 TeV

Measurements of the sphericity of primary charged particles in minimum bias proton–proton collisions at s√=0.9, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is measured in the plane perpendicular to the beam direction using primary charged tracks with p T>0.5 GeV/c in |η|<0.8. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity (N ch) is reported for events with different p T scales (“soft” and “hard”) defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low N ch, whereas the event generators show an opposite tendency. The combined study of the sphericity and the mean p T with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators

Federated Authentication and Authorization Infrastructure for LSDMA

Within the Federated Identity Management work package of DSIT we analysed the requirements of our users regarding federated authentication and authorization components. Based on these components an integrative architecture was developed. Several pilots have been implemented to demonstrate the feasibility and general usefulness of the proposed framework. The LSDMA AAI includes bridging between SAML, OIDC and X.509 infrastructures as well as support for console access for traditionally web-oriented protocols like SAML and OIDC

Combining the X.509 and the SAML Federated Identity Management Systems

Every distributed computing infrastructure requires authentication and authorisation infrastructures (AAI) to manage access to resources and content. Several of such so called AAI systems are in use within different groups of users. In the Large Scale Data Management and Analysis project we aim to support and bring together many user communities. We therefore need to harmonise the currently used AAI systems. The approach described is to translate between different authentication systems. We furthermore try to maintain the same trust level wherever possible, and to harmonise authorisation across the involved systems