TY - JOUR A1 - Akshat, Puri A1 - Aaboud, M. A1 - Aad, G. A1 - Abbott, B. A1 - Abdinov, O. A1 - Abeloos, B. A1 - Abhayasinghe, D. K. A1 - Abidi, S. H. A1 - Abou Zeid, O. S. A1 - Abraham, N. L. A1 - Abramowicz, H. A1 - Abreu, H. A1 - Abulaiti, Y. A1 - Acharya, B. S. A1 - Adachi, S. A1 - Adam, L. A1 - Adamczyk, L. A1 - Adelman, J. A1 - Adersberger, M. A1 - Adiguzel, A. A1 - Adye, T. A1 - Affolder, A. A. A1 - Afik, Y. A1 - Agheorghiesei, C. A1 - Aguilar-Saavedra, J. A. A1 - Ahmadov, F. A1 - Aiellil, G. A1 - Akatsuka, S. A1 - Akesson, T. P. A. A1 - Akilli, E. A1 - Akimov, A. V. A1 - Alberghi, G. L. A1 - Albert, J. A1 - Albicocco, P. A1 - Alconada Verzini, M. J. A1 - Alderweireld, S. A1 - Aleksa, M. A1 - Aleksandrov, I. N. A1 - Alexa, C. A1 - Alexopoulos, T. A1 - Alhroob, M. A1 - Ali, B. A1 - Alimonti, G. A1 - Alison, J. A1 - Andre, S. P. A1 - Allaire, C. A1 - Allbrooke, B. M. M. A1 - Allen, B. W. A1 - Allport, P. P. A1 - Aloisio, A. A1 - Alonso, A. A1 - Alonso, F. A1 - Alpigiani, C. A1 - Alshehri, A. A. A1 - Alstaty, M. I. A1 - Alvarez, Gonzalez B. A1 - Alvarez Piqueras, D. A1 - Alviggi, M. G. A1 - Amadio, B. T. A1 - Amaral, Coutinho, Y. A1 - Ambler, A. A1 - Ambroz, L. A1 - Amelung, C. A1 - Amidei, D. A1 - Amor Dos Santos, S. P. A1 - Amoroso, S. A1 - Amrouche, C. S. A1 - Anastopoulos, C. A1 - Ancu, L. S. A1 - Andari, N. A1 - Andeen, T. A1 - Anders, C. F. A1 - Anders, J. K. A1 - Anderson, K. J. A1 - Andreazza, A. A1 - Andrei, V. A1 - et al, T1 - Measurement of angular and momentum distributions of charged particles within and around jets in Pb plus Pb and pp collisions at root s(NN)=5.02 TeV with ATLAS at the LHC : XXVIIth International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 2018) JF - Nuclear Physics A N2 - Studies of the fragmentation of jets into charged particles in heavy-ion collisions can help in understanding the mechanism of jet quenching by the hot and dense QCD matter created in such collisions, the quark-gluon plasma. These proceedings present a measurement of the angular distribution of charged particles around the jet axis in root s(NN) = 5.02 TeV Pb+Pb and pp collisions, done using the ATLAS detector at the LHC. The measurement is performed inside jets reconstructed with the anti-k(t) algorithm with radius parameter R = 0.4, and is extended to regions outside the jet cone. Results are presented as a function of Pb+Pb collision centrality, and both jet and charged-particle transverse momenta. KW - jets KW - fragmentation functions KW - jet shapes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224703 VL - 982 IS - 2 ER - TY - JOUR A1 - Schrewe, L. A1 - Lill, C. M. A1 - Liu, T. A1 - Salmen, A. A1 - Gerdes, L. A. A1 - Guillot-Noel, L. A1 - Akkad, D. A. A1 - Blaschke, P. A1 - Graetz, C. A1 - Hoffjan, S. A1 - Kroner, A. A1 - Demir, S. A1 - Böhme, A. A1 - Rieckmann, P. A1 - El Ali, A. A1 - Hagemann, N. A1 - Hermann, D. M. A1 - Cournu-Rebeix, I. A1 - Zipp, F. A1 - Kümpfel, T. A1 - Buttmann, M. A1 - Zettl, U. K. A1 - Fontaine, B. A1 - Bertram, L. A1 - Gold, R. A1 - Chan, A. T1 - Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS JF - Journal of Neuroinflammation N2 - Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods: MOG\(_{35-55}\) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE\(^{-/-}\)) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE\(^{-/-}\) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease. KW - immune KW - apoE KW - gender KW - inflammation KW - association studies in genetics KW - apoe KW - CNS disease KW - system KW - multiple sclerosis KW - MSSS KW - experimental autoimmune encephalomyelitis KW - disease severity KW - cognitive function KW - Alzheimer disease Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136252 VL - 12 IS - 234 ER - TY - JOUR A1 - Trafimow, David A1 - Amrhein, Valentin A1 - Areshenkoff, Corson N. A1 - Barrera-Causil, Carlos J. A1 - Beh, Eric J. A1 - Bilgiç, Yusuf K. A1 - Bono, Roser A1 - Bradley, Michael T. A1 - Briggs, William M. A1 - Cepeda-Freyre, Héctor A. A1 - Chaigneau, Sergio E. A1 - Ciocca, Daniel R. A1 - Correa, Juan C. A1 - Cousineau, Denis A1 - de Boer, Michiel R. A1 - Dhar, Subhra S. A1 - Dolgov, Igor A1 - Gómez-Benito, Juana A1 - Grendar, Marian A1 - Grice, James W. A1 - Guerrero-Gimenez, Martin E. A1 - Gutiérrez, Andrés A1 - Huedo-Medina, Tania B. A1 - Jaffe, Klaus A1 - Janyan, Armina A1 - Karimnezhad, Ali A1 - Korner-Nievergelt, Fränzi A1 - Kosugi, Koji A1 - Lachmair, Martin A1 - Ledesma, Rubén D. A1 - Limongi, Roberto A1 - Liuzza, Marco T. A1 - Lombardo, Rosaria A1 - Marks, Michael J. A1 - Meinlschmidt, Gunther A1 - Nalborczyk, Ladislas A1 - Nguyen, Hung T. A1 - Ospina, Raydonal A1 - Perezgonzalez, Jose D. A1 - Pfister, Roland A1 - Rahona, Juan J. A1 - Rodríguez-Medina, David A. A1 - Romão, Xavier A1 - Ruiz-Fernández, Susana A1 - Suarez, Isabel A1 - Tegethoff, Marion A1 - Tejo, Mauricio A1 - van de Schoot, Rens A1 - Vankov, Ivan I. A1 - Velasco-Forero, Santiago A1 - Wang, Tonghui A1 - Yamada, Yuki A1 - Zoppino, Felipe C. M. A1 - Marmolejo-Ramos, Fernando T1 - Manipulating the Alpha Level Cannot Cure Significance Testing JF - Frontiers in Psychology N2 - We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable. KW - statistical significance KW - null hypothesis testing KW - p-value KW - significance testing KW - decision making Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189973 SN - 1664-1078 VL - 9 IS - 699 ER - TY - JOUR A1 - Müller, Stefanie H. A1 - Girard, Simon L. A1 - Hopfner, Franziska A1 - Merner, Nancy D. A1 - Bourassa, Cynthia V. A1 - Lorenz, Delia A1 - Clark, Lorraine N. A1 - Tittmann, Lukas A1 - Soto-Ortolaza, Alexandra I. A1 - Klebe, Stephan A1 - Hallett, Mark A1 - Schneider, Susanne A. A1 - Hodgkinson, Colin A. A1 - Lieb, Wolfgang A1 - Wszolek, Zbigniew K. A1 - Pendziwiat, Manuela A1 - Lorenzo-Betancor, Oswaldo A1 - Poewe, Werner A1 - Ortega-Cubero, Sara A1 - Seppi, Klaus A1 - Rajput, Alex A1 - Hussl, Anna A1 - Rajput, Ali H. A1 - Berg, Daniela A1 - Dion, Patrick A. A1 - Wurster, Isabel A1 - Shulman, Joshua M. A1 - Srulijes, Karin A1 - Haubenberger, Dietrich A1 - Pastor, Pau A1 - Vilariño-Güell, Carles A1 - Postuma, Ronald B. A1 - Bernard, Geneviève A1 - Ladwig, Karl-Heinz A1 - Dupré, Nicolas A1 - Jankovic, Joseph A1 - Strauch, Konstantin A1 - Panisset, Michel A1 - Winkelmann, Juliane A1 - Testa, Claudia M. A1 - Reischl, Eva A1 - Zeuner, Kirsten E. A1 - Ross, Owen A. A1 - Arzberger, Thomas A1 - Chouinard, Sylvain A1 - Deuschl, Günther A1 - Louis, Elan D. A1 - Kuhlenbäumer, Gregor A1 - Rouleau, Guy A. T1 - Genome-wide association study in essential tremor identifies three new loci JF - Brain N2 - We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor. KW - quality-control KW - disease KW - tool KW - movement disorders KW - genome-wide association study KW - tremor KW - genetics KW - essential tremor Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186541 VL - 139 ER - TY - JOUR A1 - Sodemann, Elisa B. A1 - Dähling, Sabrina A1 - Klopfleisch, Robert A1 - Boiarina, Ekaterina A1 - Cataldo, Didier A1 - Alhasan, Moumen M. A1 - Yildirim, Ali Ö. A1 - Witzenrath, Martin A1 - Tabeling, Christoph A1 - Conrad, Melanie L. T1 - Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation JF - Clinical & Experimental Allergy N2 - Background Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro‐ or anti‐inflammatory manner depending on their glycosylation status. Objective Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. Methods Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn‐297 IgG glycosylation was analysed in maternal and offspring serum. Results When mothers and offspring were sensitized to the same allergen (OVA‐OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS‐OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro‐inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn‐297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. Conclusions and Clinical Relevance We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro‐inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies. KW - allergic airway inflammation KW - asthma risk KW - IgG glycosylation KW - maternal asthma KW - pregnancy KW - sialylation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214071 VL - 50 IS - 4 SP - 520 EP - 531 ER -