Oscillatory behaviour of the RBF-FD approximation accuracy under increasing stencil size

When solving partial differential equations on scattered nodes using the Radial Basis Function generated Finite Difference (RBF-FD) method, one of the parameters that must be chosen is the stencil size. Focusing on Polyharmonic Spline RBFs with monomial augmentation, we observe that it affects the approximation accuracy in a particularly interesting way - the solution error oscillates under increasing stencil size. We find that we can connect this behaviour with the spatial dependence of the signed approximation error. Based on this observation we are then able to introduce a numerical quantity that indicates whether a given stencil size is locally optimal.Comment: 8 pages, 6 figures, ICCS 2023 Conference Pape

Disease-modifying therapy for multiple sclerosis in Slovenia: analysis of 20 years of treatment

Introduction: Disease-modifying therapy (DMT) dramatically influenced the management of re- lapsing-remitting multiple sclerosis (RRMS). Novel medicines have been developing constantly and therapeutic strategy has changed. We aimed to analyse the development of DMT for MS in Slovenia with a special emphasis on contemporary approaches to the patient management. Materials and Methods: Prescriptions of all DMT in Slovenia from 2001-2021 were analysed as well as re- ferrals to the Committee for MS DMT the Centre for MS in Ljubljana in the last three years (2019-2021). Results: Altogether approximately 360 patients were on DMT in 2001 and 1839 in 2021. The total number of patients on injectable therapies decreased through time while the number of patients on oral therapies increased. Dimethyl fumarate is currently the most frequently used medicine with 505 patients on the drug in 2021. The number of patients on potent medications increased from 28 (3%) in 2012 to 763 (41%) in 2021. Highly active medicines represented 52%, 62% and 69% of all DMT approvals in 2019, 2020 and 2021, respectively. Conclusions: The number of treated MS patients has been increasing steadily in Slovenia as well as the number of patients on potent DMT which proves that neurologists follow the modern concept of MS treatment

Disease-modifying therapy for multiple sclerosis in Slovenia: analysis of 20 years of treatment

Introduction: Disease-modifying therapy (DMT) dramatically influenced the management of re- lapsing-remitting multiple sclerosis (RRMS). Novel medicines have been developing constantly and therapeutic strategy has changed. We aimed to analyse the development of DMT for MS in Slovenia with a special emphasis on contemporary approaches to the patient management. Materials and Methods: Prescriptions of all DMT in Slovenia from 2001-2021 were analysed as well as re- ferrals to the Committee for MS DMT the Centre for MS in Ljubljana in the last three years (2019-2021). Results: Altogether approximately 360 patients were on DMT in 2001 and 1839 in 2021. The total number of patients on injectable therapies decreased through time while the number of patients on oral therapies increased. Dimethyl fumarate is currently the most frequently used medicine with 505 patients on the drug in 2021. The number of patients on potent medications increased from 28 (3%) in 2012 to 763 (41%) in 2021. Highly active medicines represented 52%, 62% and 69% of all DMT approvals in 2019, 2020 and 2021, respectively. Conclusions: The number of treated MS patients has been increasing steadily in Slovenia as well as the number of patients on potent DMT which proves that neurologists follow the modern concept of MS treatment

RNAmotifs: prediction of multivalent RNA motifs that control alternative splicing

RNA-binding proteins (RBPs) regulate splicing according to position-dependent principles, which can be exploited for analysis of regulatory motifs. Here we present RNAmotifs, a method that evaluates the sequence around differentially regulated alternative exons to identify clusters of short and degenerate sequences, referred to as multivalent RNA motifs. We show that diverse RBPs share basic positional principles, but differ in their propensity to enhance or repress exon inclusion. We assess exons differentially spliced between brain and heart, identifying known and new regulatory motifs, and predict the expression pattern of RBPs that bind these motifs. RNAmotifs is available at https://bitbucket.org/rogrro/rna_motifs

A cis-regulatory element promoting increased transcription at low temperature in cultured ectothermic Drosophila cells

Background Temperature change affects the myriad of concurrent cellular processes in a non-uniform, disruptive manner. While endothermic organisms minimize the challenge of ambient temperature variation by keeping the core body temperature constant, cells of many ectothermic species maintain homeostatic function within a considerable temperature range. The cellular mechanisms enabling temperature acclimation in ectotherms are still poorly understood. At the transcriptional level, the heat shock response has been analyzed extensively. The opposite, the response to sub-optimal temperature, has received lesser attention in particular in animal species. The tissue specificity of transcriptional responses to cool temperature has not been addressed and it is not clear whether a prominent general response occurs. Cis-regulatory elements (CREs), which mediate increased transcription at cool temperature, and responsible transcription factors are largely unknown. Results The ectotherm Drosophila melanogaster with a presumed temperature optimum around 25 °C was used for transcriptomic analyses of effects of temperatures at the lower end of the readily tolerated range (14–29 °C). Comparative analyses with adult flies and cell culture lines indicated a striking degree of cell-type specificity in the transcriptional response to cool. To identify potential cis-regulatory elements (CREs) for transcriptional upregulation at cool temperature, we analyzed temperature effects on DNA accessibility in chromatin of S2R+ cells. Candidate cis-regulatory elements (CREs) were evaluated with a novel reporter assay for accurate assessment of their temperature-dependency. Robust transcriptional upregulation at low temperature could be demonstrated for a fragment from the pastrel gene, which expresses more transcript and protein at reduced temperatures. This CRE is controlled by the JAK/STAT signaling pathway and antagonizing activities of the transcription factors Pointed and Ets97D. Conclusion Beyond a rich data resource for future analyses of transcriptional control within the readily tolerated range of an ectothermic animal, a novel reporter assay permitting quantitative characterization of CRE temperature dependence was developed. Our identification and functional dissection of the pst_E1 enhancer demonstrate the utility of resources and assay. The functional characterization of this CoolUp enhancer provides initial mechanistic insights into transcriptional upregulation induced by a shift to temperatures at the lower end of the readily tolerated range

iCLIP - Transcriptome-wide Mapping of Protein-RNA Interactions with Individual Nucleotide Resolution

The unique composition and spatial arrangement of RNA-binding proteins (RBPs) on a transcript guide the diverse aspects of post-transcriptional regulation1. Therefore, an essential step towards understanding transcript regulation at the molecular level is to gain positional information on the binding sites of RBPs2

Conserved developmental transcriptomes in evolutionarily divergent species

Transcriptional profiling of Dictyostelium development reveals significant conservation of transcriptional profiles between evolutionarily divergent species

SNPsyn: detection and exploration of SNP–SNP interactions

SNPsyn (http://snpsyn.biolab.si) is an interactive software tool for the discovery of synergistic pairs of single nucleotide polymorphisms (SNPs) from large genome-wide case-control association studies (GWAS) data on complex diseases. Synergy among SNPs is estimated using an information-theoretic approach called interaction analysis. SNPsyn is both a stand-alone C++/Flash application and a web server. The computationally intensive part is implemented in C++ and can run in parallel on a dedicated cluster or grid. The graphical user interface is written in Adobe Flash Builder 4 and can run in most web browsers or as a stand-alone application. The SNPsyn web server hosts the Flash application, receives GWAS data submissions, invokes the interaction analysis and serves result files. The user can explore details on identified synergistic pairs of SNPs, perform gene set enrichment analysis and interact with the constructed SNP synergy network

Characterising the RNA targets and position-dependent splicing regulation by TDP-43: implications for neurodegenerative diseases

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