86,616 research outputs found
A. F. Puukko, Rafael Gyllenberg ja E. G. Gulin Raamatun tietokirja II
No full textKirja-arvioPuukko, A. F. & Gyllenberg, Rafael & Gulin, E. G.: Raamatun tietokirja I
Genetic studies of complex autoimmune disease
No full textIn complex autoimmune diseases, there are both genetic and environmental factors that influence our immune system and contribute to the development of disease. The pathways, interactions and mode of inheritance are difficult to unravel, and many discoveries are yet to be done. Here, I have studied three major autoimmune diseases, Type 1 Diabetes (T1D), Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA). They all have an inflammatory component, and share their genetic predisposition in the Human Leucocyte Antigen (HLA) genes. In T1D, the -cells in the pancreatic Islets of Langerhans are very specifically destroyed in an autoimmune attack, lead by the CD8+ T-cells. This leads to the inability to produce insulin, and a lifelong treatment with daily injections is necessary. The elevated blood glucose levels leads to long-term damages of microvascular circulations, and co-morbidities like neuropathy and cardiovascular disease. In MS, auto-reactive lymphocytes enter the central nervous system (CNS) and causes demyelination and neuronal damage. It results in a periodical occurrence of sclerotic plaques in the brain and spinal cord, and leads to increasing neurological disability. RA is a systemic inflammatory disease induced by activation of auto-reactive T-cells, where the release of antibodies and formation of immune complexes contributes to the severity in anti-citrullinated protein antibody (ACPA) positive but not ACPA negative disease. The target tissue is the synovial joints, but other organs like heart and kidney will also be affected. The inflammation breaks down cartilage and bone and can lead to severe pain and disability.In this thesis I present my investigations of two candidate genes, CIITA and VAV1, in these diseases. CIITA is the major control factor for transcription of the HLA class II genes, and associated to all three diseases. In paper I we demonstrate genotype variation for markers in the CIITA gene, depending on age among healthy controls. This finding is also replicated in an independent cohort. The consequence of this can be faulty conclusions in association studies, and hence age should be corrected for in genetic case-control studies. We find that association to T1D remains after controlling for age for rs11074932 (p=0.004) and rs3087456 (p=0.001), two markers in the promoter area that also are found to associate to RA but for the opposite allele (paper III). In paper II we replicate the previously reported association between CIITA rs4774 and MS in cases carrying the HLA-DRB1*15 allele (p=0.01, OR: 1.21) but also report association to MS for the same marker when stratifying for the MS protective HLA allele A*02 (p=0.01, OR: 1.33). Interaction between rs4774 and both MS associated HLA alleles is demonstrated. Finally, in paper III we show that the markers found to associate to T1D, MS and RA control the expression of CIITA and MHC class II genes with minor allele homozygotes leading to lower levels of mRNA of the transcripts. In paper IV we investigate the VAV1 gene, important in regulating signals downstream the T-cell receptor. VAV1 has been shown to associate to MS and lead to increased levels of inflammatory cytokines in the CNS. Here we report that the same rs2546133-rs2617822 C-A haplotype is associated only to the ACPA negative subgroup of Rheumatoid Arthritis (p=0.004, OR: 1.28). We also demonstrate that a SNP in the Vav1 gene in rat affects disease severity in pristane-induced arthritis, but not collagen II-induced arthritis, such that the disease in PIA is less severe.Taken together we suggest that these results for VAV1 reflect the heterogeneity between subgroups in human RA disease. In conclusion I have demonstrated genetic susceptibility factors and pathways that are shared between different autoimmune diseases but also that susceptibility genes can be of different importance in subgroups of patients for one disease.List of scientific papersI. Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes. A Gyllenberg, S Asad, F Piehl, M Swanberg, L Padyukov, B Van Yserloo, EA Rutledge, B McNeney, J Graham, M Orho-Melander, E Lindholm, C Graff, C Forsell, K Åkesson, M Landin-Olsson, A Carlsson, G Forsander, SA Ivarsson, H Larsson, B Lindblad, J Ludvigsson, C Marcus, Å Lernmark, L Alfredsson, K Åkesson, T Olsson, I Kockum, the Swedish Childhood Diabetes Study Group, the Diabetes Incidence in Sweden Study Group, and the Better Diabetes Diagnosis Study group. Genes and Immunity. (2012) 13, 632–40. https://doi.org/10.1038/gene.2012.44 II. Variability in the CIITA gene interacts with HLA in multiple sclerosis. A Gyllenberg, F Piehl, L Alfredsson, J Hillert, IL Bomfim, L Padyukov, M Orho Melander, E Lindholm, M Landin-Olsson, Å Lernmark, The Swedish Childhood Diabetes Study Group, The Diabetes Incidence in Sweden Study Group, T Olsson and I Kockum. Genes and Immunity. (2014), 1–6. https://doi.org/10.1038/gene.2013.71 III. Genetic control of isoform expression of human MHC class II transactivator. M Ronninger, A Gyllenberg, M Lindén, M Seddighzadeh, T James, S K Bedri, D Gomez-Cabrero, F Piehl, T Olsson, I Kockum, L Padyukov. [Manuscript]IV. VAV1 shows association to anti-citrullinated protein antibody (ACPA) negative Rheumatoid Arthritis in a Swedish patient cohort. Ulrika Norin, André Ortlieb Guerreiro-Cacais, Alexandra Gyllenberg, Rasmus Berglund, Amennai Daniel Beyeen, Rikard Holmdahl, Elisabeth Petit Teixeira, François Cornélis, Abdelhadi Saoudi, Gilbert J. Fournié, Leonid Padyukov, Ingrid Kockum, Maja Jagodic and Tomas Olsson. [Manuscript]</p
Pseudospectral discretization of nonlinear delay equations: new prospects for numerical bifurcation analysis
No full textWe apply the pseudospectral discretization approach to nonlinear delay models described by delay differential equations, renewal equations or systems of coupled renewal equations and delay differential equations. The aim is to derive ordinary differential equations and to investigate the stability and bifurcation of equilibria of the original model by available software packages for continuation and bifurcation for ordinary differential equations. Theoretical and numerical results confirm the effectiveness and the versatility of the approach, opening a new perspective for the bifurcation analysis of delay equations, in particular coupled renewal and delay differential equations
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
John F. Kennedy telegram to Roosevelt
No full textJersey Homesteads (later the Borough of Roosevelt) was established in the 1930s as an agro-industrial cooperative community. It was established specifically for urban Jewish garment workers, many of whom had emigrated from Europe. President John F. Kennedy sent a telegram to the citizens of Roosevelt, New Jersey, apologizing for not being able to attend the memorial dedication in honor of former President Franklin Delano Roosevelt. (Jersey Homesteads became Roosevelt in 1945 in honor of the president.) President Kennedy expressed his gratitude to the people of Roosevelt for constructing the memorial, and commented that it will serve as a constant reminder of Roosevelt's good works
Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
No full textWe report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Maine author Franklin F. Gould recalls his first glimpse of the outside world
No full textMaine author Franklin F. Gould recalls his first glimpse of the outside world as he relates how, as a young farm boy in the late 1800\u27s, he drove his father\u27s horses on an errand to an icebound river
Mapping the Discipline of the Olympic Games An Author-Cocitation Analysis
No full textThe authors conducted an author cocitation analysis on prominent authors writing about the Olympics during the 1990s. Author cocitation is an established bibliometric technique that can be used to measure the relative similarities of topics written about by the cited authors. This enables a visual representation of the “intellectual space” of the discipline, in this case the Olympics, to be created for the period under review. So core and peripheral research areas are identified, along with their major contributors. The representation appears as a two-dimensional cluster-enhanced map. Subject expertise was then applied to the results to place labels on the generated clusters of authors and their topics
- …
