Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

in Nature Genetics (2017), 49

Rare gene deletions in genetic generalized and Rolandic epilepsies

in PLoS ONE (2018)

Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as ... [more ▼]

Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as important risk factors in brain disorders. We performed a systematic survey of rare deletions affecting protein-coding genes derived from exome data of patients with common forms of genetic epilepsies. We analysed exomes from 390 European patients (196 GGE and 194 RE) and 572 population controls to identify low-frequency genic deletions. We found that 75 (32 GGE and 43 RE) patients out of 390, i.e. ~19%, carried rare genic deletions. In particular, large deletions (>400 kb) represent a higher burden in both GGE and RE syndromes as compared to controls. The detected low-frequency deletions (1) share genes with brain-expressed exons that are under negative selection, (2) overlap with known autism and epilepsy-associated candidate genes, (3) are enriched for CNV intolerant genes recorded by the Exome Aggregation Consortium (ExAC) and (4) coincide with likely disruptive de novo mutations from the NPdenovo database. Employing several knowledge databases, we discuss the most prominent epilepsy candidate genes and their protein-protein networks for GGE and RE. [less ▲]

Rare variant analysis of the PPMI dataset to uncover the complex genetic architecture of Parkinson’s disease

in Movement Disorders (2017, June 02), 322(Supplement S2), 405

Objective: To unravel the genetic factors that play a role in PD we used the whole exome sequencing data available as a part of Parkinson Progression Markers Initiative (PPMI). Background: Parkinson’s ... [more ▼]

Objective: To unravel the genetic factors that play a role in PD we used the whole exome sequencing data available as a part of Parkinson Progression Markers Initiative (PPMI). Background: Parkinson’s disease (PD) is a complex disease. Besides variants in high-risk genes such as LRRK2 and PARK2, multiple genes associated to sporadic PD were discovered via genome-wide association studies. Yet, there is a large number of genetic factors that need to be deciphered. Methods: To unravel the genetic factors that play a role in PD we used the whole exome sequencing data available as a part of Parkinson Progression Markers Initiative (PPMI). The dataset comprised of 435 PD cases and 162 ethnically matched controls, respectively. We performed burden tests at single variant, gene and geneset levels on common and rare exonic and splice-variants. We also looked for severity of rare highly deleterious variants (CADD phred score>30) using the CADD score as well as singleton (variants seen in only one individual across cases and controls) rare variants. Additionally, we performed the functional enrichment analysis with the genes harboring rare highly deleterious variants (case uniq genes) that are only present in cases. Results: We observed an increased mutational burden of singleton variants in PD cases compared to the controls in nonsynonymous+LOF variants (empirical P-value 0.005) but not in the synonymous variants (empirical P-value 0.09). We observed a higher significant burden (P-value 0.028) as well as higher significant severity (empirical P-value 0.027) of rare, highly deleterious nonsynonymous variants, but not in the synonymous variants of the candidate genes (P-value 0.686, empirical P-value 0.556 for burden and severity respectively). The network analysis of genes having deleterious variants only present in cases (Case uniq) showed a significant increase in connectivity compared to random networks (P-value 0.0002). Pathway analysis of those genes showed a significant enrichment of pathways and biological process implicated in the nervous system functioning and the etiology of PD. Conclusions: Our study supports the complex disease notion of PD by highlighting the convoluted architecture of PD where case uniq genes including LRRK2 are implicated in several biological processes and pathways related to PD. The main finding of this study is to discover the complex genetics of PD at an exome wide level. [less ▲]

Ras-association domain family member 1A (RASSF1A)-where the heart and cancer meet.

in Trends in cardiovascular medicine (2009), 19(8), 262-7

The close relationship between signaling pathways regulating tumor growth and cardiac hypertrophy has attracted considerable interest. Although the involvement of proto-oncogenes in positively modulating ... [more ▼]

The close relationship between signaling pathways regulating tumor growth and cardiac hypertrophy has attracted considerable interest. Although the involvement of proto-oncogenes in positively modulating myocardial hypertrophy has long been recognized, little is known about factors that counterregulate them. In this article, we review the novel tumor suppressor Ras-association domain family protein isoform 1A (RASSF1A), which strongly inhibits the prohypertrophic Ras-Raf1-ERK1/2 pathway in the heart. RASSF1A interacts with a number of important signaling molecules regulating cell growth, survival, and apoptosis; therefore, it serves as a key adaptor molecule that integrates the upstream stimuli and transduces them to the selective downstream effectors. [less ▲]

Rassismus an Diskriminatioun

Speeches/Talks (2018)

Die rassismussensible Schule - ein Vorwort

in Böhmer, Matthias; Steffgen, Georges (Eds.) Rassismus an Schulen - Geschichte, Erklärungen, Auswirkungen und Interventionsansätze (2022)

RAT: A Referencing and Annotation Tool for Digitized Early Maps

Scientific Conference (2016, June)

RAT is designed to support users in identifying place markers in digitised early maps and to link these place markers to modern maps. RAT facilitates a geo-referencing by suggesting the most likely modern ... [more ▼]

RAT is designed to support users in identifying place markers in digitised early maps and to link these place markers to modern maps. RAT facilitates a geo-referencing by suggesting the most likely modern places based on an estimated mapping and a phonetic search for place names. [less ▲]

Rate of estimation for the stationary distribution of jump-processes over anisotropic Holder classes.

E-print/Working paper (2020)

We study the problem of the non-parametric estimation for the density π of the stationary distribution of the multivariate stochastic differential equation with jumps (Xt)0≤t≤T , when the dimension d is ... [more ▼]

We study the problem of the non-parametric estimation for the density π of the stationary distribution of the multivariate stochastic differential equation with jumps (Xt)0≤t≤T , when the dimension d is such that d ≥ 3. From the continuous observa- tion of the sampling path on [0, T ] we show that, under anisotropic H ̈older smoothness constraints, kernel based estimators can achieve fast convergence rates. In particu- lar, they are as fast as the ones found by Dalalyan and Reiss [9] for the estimation of the invariant density in the case without jumps under isotropic H ̈older smooth- ness constraints. Moreover, they are faster than the ones found by Strauch [29] for the invariant density estimation of continuous stochastic differential equations, under anisotropic H ̈older smoothness constraints. Furthermore, we obtain a minimax lower bound on the L2-risk for pointwise estimation, with the same rate up to a log(T) term. It implies that, on a class of diffusions whose invariant density belongs to the anisotropic Holder class we are considering, it is impossible to find an estimator with a rate of estimation faster than the one we propose. [less ▲]

Rate Splitting Multiple Access for Cognitive Radio GEO-LEO Co-Existing Satellite Networks

Scientific Conference (2022, December 07)

Low Earth orbit (LEO) satellite communication has drawn particular attention recently due to its high data rate services and low round-trip latency. It is low-cost to launch and can provide global ... [more ▼]

Low Earth orbit (LEO) satellite communication has drawn particular attention recently due to its high data rate services and low round-trip latency. It is low-cost to launch and can provide global coverage. However, the spectrum scarcity might be one of the critical challenges in the growth of LEO satellites, impacting severe restrictions on the development of ground-space integrated networks. To address this issue, we propose rate splitting multiple access (RSMA) for cognitive radio (CR) enabled nongeostationary orbit (GEO)-LEO coexisting satellite network. In particular, this work aims to maximize the system's sum rate by simultaneously optimizing the power allocation and subcarrier beam assignment of LEO satellite communication while restricting the interference temperature to GEO satellite users. The problem of sum rate maximization is formulated as non-convex and a Global optimal solution is challenging to obtain. Therefore, we first employ the successive convex approximation technique to reduce the complexity and make the problem more tractable. Then for the power allocation, we exploit Karush–Kuhn–Tucker (KKT) condition and adopt an efficient algorithm based on the greedy approach for subcarrier beam assignment. We also propose two suboptimal schemes with fixed power allocation and random subcarrier beam assignment. [less ▲]

Rate-dependent phase-field damage modeling of rubber and its experimental parameter identification

in Journal of the Mechanics and Physics of Solids (2019)

Phase-field models have the advantage in that no geometric descriptions of cracks are required, which means that crack coalescence and branching can be treated without additional effort. Miehe and ... [more ▼]

Phase-field models have the advantage in that no geometric descriptions of cracks are required, which means that crack coalescence and branching can be treated without additional effort. Miehe and Schänzel (2014) introduced a rate-independent phase-field damage model for finite strains in which a viscous damage regularization was proposed. We extend the model to depend on the loading rate and time by incorporating rubber’s strain-rate dependency in the constitutive description of the bulk, as well as in the damage driving force. The parameters of the model are identified using experiments at different strain rates. Local strain fields near the crack tip, obtained with digital image correlation (DIC), are used to help identify the length scale parameter. Three different degradation functions are assessed for their accuracy to model the rubber’s rate-dependent fracture. An adaptive time-stepping approach with a corrector scheme is furthermore employed to increase the computational efficiency with a factor of six, whereas an active set method guarantees the irreversibility of damage. Results detailing the energy storage and dissipation of the different model constituents are included, as well as validation results that show promising capabilities of rate-dependent phase-field modeling. [less ▲]