Locally univalent functions, VMOA, and the Dirichlet space

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Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Kirkkodraama Hyvinkäällä : omakohtaisesti koettuna

Opinnäytetyö lähtee liikkeelle kirkkodraaman alkujuurilta, etsien kirkkodraaman kansainväliseen syntyyn liittyviä seikkoja ja edeten kohti kirkkodraaman rantautumista Suomeen ja kehitystä tämän päivän kirkkodraamaksi. Miten kirkkodraamaan liittyvä koulutus on käynnistynyt. Millaista kehitystä ja havaintoja on Suomessa toteutetussa kirkkodraamassa tapahtunut viime vuosikymmenillä ja mitä on tapahtunut 1980-, 1990- ja 2000-luvuilla Hyvinkäällä toteutetussa kirkkodraamatyöskentelyssä. Opinnäytetyö kartoittaa, millaisia kirkkodraaman lajityyppejä on ja miten niitä on Hyvinkäällä toteutettu, kuinka niiden tekemiseen on päädytty. Millaisia vaiheita kirkkodraaman ohjaustyön ammatillistumisessa on ollut omalla kohdallani ja miten se on ollut havaittavissa eri vuosikymmeninä Hyvinkäällä ja millainen oli kirkkoteatterin kiirastuli 2001, jolloin kirkkoteatterityön tulevaisuus oli hyvinkääläisten kirkkohallintoelinten ruodittavana ja miten se siitä selvisi. Opinnäytetyötä varten tein luettelon kaikista Hyvinkään seurakunnalle toteuttamistani kirkkodraamoista, joita opinnäytetyöhön 15.11.2006 mennessä oli kertynyt tasan 100 kirkkodraamaa. Tämä luettelo on opinnäytetyön liitteenä. Luetteloon on merkitty jokaisen näytelmän kohdalle mitä lajityyppiä teos edustaa.

Modulaarisen työasemaohjelmiston Testauksen automatisointi

Opinnäytetyön aiheena oli tutkia modulaarisen työasemaohjelmiston automatisoinnin mahdollisuuksia ja niiden toteuttamista käytännössä. Teoriaosuudessa käsitellään ohjelmistotestauksen ja automatisoinnin peruskäsitteitä. Suurin osa työstä keskittyy testitapausten suunnitteluun, toteutukseen ja automatisointiin. Varsinaiset automatisointitoimet keskittyvät ohjelmiston laskennan toteuttavien moduulien testauksen automatisointiin. Testaustyökaluna käytettiin TestReflector nimistä apuohjelmaa, joka on yrityksen kehittämä työkalu ohjelmistokomponenttien testaukseen. Jokaisen laskentatyypin testausta varten luotiin oma testiympäristö, joka kirjoitettiin C#- kielellä. Testiympäristön tärkein tehtävä oli alustaa tarvittavat tietorakenteet mittaustuloksilla ennen laskentojen suorittamista. Laskentojen testaukseen tarvittavat mittaustulokset saatiin laboratorioinstrumentilta. Mittaustulokset tuotiin testiympäristöön ohjelmiston käyttämästä tietokannasta XML-tiedostona.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Bysanttilainen arkkitehtuuri valtakunnan laidalla : Venetsian Markuksen kirkko suomalaisten ja ruotsalaisten 1800-luvun kirjoittajien tulkitsemana

Timo Tuomi

Weed control trials with fibre mulch, glyphosate and terbuthylazine in Scots pine plantations

Summary