Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Burner systems for glass melting furnaces with recuperative air preheating

Five different burners on an industrial scale were investigated, a standard burner and a staged burner being in industrial operation, as well as a new staged burner, a new flameless oxidation burner and an oxy-fuel burner. Α comparison of heat transfer from airfuel flames with intensified heat transfer and oxy-fuel flames was carried out. The results clearly indicate that with the new burner technology it is possible to reduce the ΝΟx emission drastically, so that the 500 mg/m3 ΝΟx limit can be achieved at glass melting furnaces. With the new burners one can obtain the same size of flames as with conventional burners. The results obtained with different heat flux measurement techniques indicate that the heat flux of the new burners is in the same range as that of the conventional burner. The project yielded extensive data for characterizing the flames and the suitability of the burners for different types of glass and glass furnaces. In addition, the experimental results serve as comparison data for mathematical modeling validation

Trichostatin A effectively induces apoptosis in chronic lymphocytic leukemia cells via inhibition of Wnt signaling and histone deacetylation

Background T he ontogenetic Wnt pathway shows almost no activity in adult tissues. In contrast, chronic lymphocytic leukemia (CLL) cells show constitutionally active Wnt signaling, which is associated with upregulated levels of pathway members such as Wnt3 and lymphoid enhancer-binding factor-1. Functionally, this results in increased resistance to apoptosis. We therefore assumed that targeting members of the pathway could reveal new therapeutic options for the treatment of CLL. Methods Screening a Wnt compound library with 75 Wnt modulators via AT P assay revealed Trichostatin A as an outstanding substance with strong viability decreasing effects on CLL cells and little effect on healthy peripheral blood mononuclear cells (PBMCs). Further survival analysis was performed via fluorescence-activated cell sorting analysis. Results A maximum effect was achieved after 48 h with a wide therapeutic window in contrast to PBMCs (CLL cells: 0.253 mu M, PBMCs: 145.22 mu M). Trichostatin A induced caspases and acted via a dual mechanism to reveal histone and non-histone targets. Histone targets were displayed in deacetylation inhibition at DNA level, and non-histone targeting was demonstrated by elevated levels of Dickkopf-related protein 1 mRNA. Primary cells of patients with critical mutations such as TP53 or those who had already undergone extensive previous treatment responded well to the treatment. Moreover, the approved histone deacetylase (HDAC) inhibitor suberoylanilidehydroxamic acid (SAHA) was not as effective as Trichostatin A (Trichostatin A: 0.253 mu M, SAHA: 7.88 mu M). Combining Trichostatin A with established CLL drugs fludarabine or bendamustine showed an additive effect in vitro. Conclusion Taken together, Trichostatin A appears to act via a dual anti-HDAC/Wnt mechanism with a high selectivity and efficacy in CLL and therefore warrants further investigation

Radiant Tube Burners

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Play at the Latvian language lessons for activating the primary school pupils’ cognitive activity

Agita Grigorjeva „Spēle latviešu valodas stundās sākumskolēna izziņas darbības aktivizēšanai.” Diplomdarbs veltīts mūsdienās aktuālam tematam – spēļu izmantošana latviešu valodas stundās, lai veicinātu skolēna izziņas darbību, radošo aktivitāti. Diplomdarba mērķis ir noskaidrot spēļu izmantošanas iespējas latviešu valodas mācību procesā vispārizglītojošās skolās skolēna izziņas darbības aktivizēšanai. Darba gaitā ir izpētīts, cik spēļu izmantošanas iespējas latviešu valodas stundās ir daudzveidīgas, tiek analizētas literārās un valodas spēles, spēles ar pierakstiem, lomu spēles u.c., un tas, kā ar to palīdzību skolēni apgūst prasmi salīdzināt, analizēt, sintezēt, vispārināt, kā spēle audzina skolēnos gribu un rosina pozitīvas emocijas mācīšanās procesā.” Play at the Latvian language lessons for activating the primary school pupils’ cognitive activity” by Agita Grigorjeva This diploma paper is devoted to the actual theme nowadays- use of plays at the Latvian language lessons to promote students’ cognitive actions and creative activity. The aim of my diploma paper is to make out possibilities of the play use at the Latvian language teaching process to activate the student’s cognitive actions in comprehensive schools. I have researched in my diploma paper, how multiform possibilities of the play use are at the Latvian language lessons.I have analysed literary and language lessons, the plays with notes, role plays and others.I have studied how students acquire skills to compare, analyse, synthesize,generalize using the plays, how the play educates will to the schoolchildren and how it promotes positive emotions at the learning process