42 research outputs found

    Evaluation of thermal and technical characteristics and energy residential building before and after insulation including prices and costs

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    Import 23/07/2015Siuda, D.: Vyhodnocení tepelně technických a energetických vlastností bytového objektu před a po zateplení včetně cen a nákladů, Ostrava VŠB – Technická univerzita Ostrava, Fakulta stavební, Katedra pozemního stavitelství 225, 2015, vedoucí práce Ing. Zdeněk Peřina, Ph.D., text 61 stran formátu A4, výkresová část obsahuje 36 výkresů. Bakalářská práce se odvíjí od projektu zpracovaného v předmětu Specializovaný projekt I a II. Práce zpracovává tepelně technické a energetické vlastnosti objektu před a po zateplení. Cílem je vypracování projektové dokumentace k povolení stavby zadaného objektu. Další součástí je vyhodnocení tepelně technických a energetických vlastností původního a zatepleného stavu objektu.Siuda, D.: Evaluation of thermal and technical characteristics and energy residential building before and after insulation including prices and costs, Ostrava VSB – Technical university of Ostrava, Faculty of civil engeneering 225, 2015, thesis supervisor Ing. Zdeněk Peřina, Ph.D., 56 pages, plus 36 drawings. Bachelor thesis derives from a project developed in the scope of Specialized Project I and II. Work processes thermal technical and energy properties of the object before and after insulation. The aim is to develop project documentation for the building permit specified object. Another part of the evaluation of thermal technical and energy properties of the original and insulated object state.225 - Katedra pozemního stavitelstvívelmi dobř

    Sports hall in Ostrava - Constructional technological project

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    Import 13/01/2017Bc. Siuda D.: Sportovní hala v Ostravě – Stavebně technologický projekt, Ostrava VŠB – Technická univerzita Ostrava, Fakulta Stavební, Katedra pozemního stavitelství 225, 2016, vedoucí práce Ing. Radek Fabián, Ph.D., text 58 stran formátu A4, výkresová část obsahuje 15 výkresů. Diplomová práce se odvíjí od projektu zpracovaného v předmětu Projekt I a II. Práce zpracovává stavebně technologický projekt sportovní haly a porovnává možné varianty stropních konstrukcí. Cílem je určit ekonomičtější a méně technologicky náročnou variantu stropní konstrukce.Bc. Siuda D.: Sports hall in Ostrava – Constructional technological project, Ostrava VSB – Technical university of Ostrava, Faculty of civil engeneering 225, 2016, thesis supervisor Ing. Radek Fabián, Ph.D., 58 pages, 15 drawings. The thesis is based on the project developed in the subject Project I and II. Work processes construction and technological project of the sports hall and compares the possible variants of floor structures. The aim is to identify more economical and less technologically demanding variant ceiling structure.225 - Katedra pozemního stavitelstvívelmi dobř

    A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

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    Introduction: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. Methods: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. Results: A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni-corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively). Discussion: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Regulation of Nox4 expression by histone deacetylases in human endothelial cells : involvement of epigenetic mechanisms

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    Nox4 is a member of the NADPH oxidase family, which represents a major source of reactive oxygen species (ROS) in the vascular wall. Nox4-mediated ROS production mainly depends on the expression levels of the enzyme. The aim of my study was to investigate the mechanisms of Nox4 transcription regulation by histone deacetylases (HDAC). Treatment of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy926 cells with the pan-HDAC inhibitor scriptaid led to a marked decrease in Nox4 mRNA expression. A similar down-regulation of Nox4 mRNA expression was observed by siRNA-mediated knockdown of HDAC3. HDAC inhibition in endothelial cells was associated with enhanced histone acetylation, increased chromatin accessibility in the human Nox4 promoter region, with no significant changes in DNA methylation. In addition, the present study provided evidence that c-Jun played an important role in controlling Nox4 transcription. Knockdown of c-Jun with siRNA led to a down-regulation of Nox4 mRNA expression. In response to scriptaid treatment, the binding of c-Jun to the Nox4 promoter region was reduced despite the open chromatin structure. In parallel, the binding of RNA polymerase IIa to the Nox4 promoter was significantly inhibited as well, which may explain the reduction in Nox4 transcription. In conclusion, HDAC inhibition decreases Nox4 transcription in human endothelial cells by preventing the binding of transcription factor(s) and polymerase(s) to the Nox4 promoter, most likely because of a hyperacetylation-mediated steric inhibition. In addition, HDAC inhibition-induced Nox4 downregulation may also involves microRNA-mediated mRNA destabilization, because the effect of the scriptaid could be partially blocked by DICER1 knockdown or by transcription inhibition.Nox4 gehört zur Familie der NADPH Oxidasen. Diese Familie ist der Hauptverursacher von ROS in den Wänden von Blutgefäßen. Die Menge von Nox4 produziertem ROS hängt hauptsächlich vom Expressionslevels des Enzyms ab. In der folgenden Studie sollten die Mechanismen der transkriptionellen Regulation der Nox4 durch Histone-Deacetylasen (HDAC) genauer erforscht werden. Die Behandlung, von menschlichen Endothelzellen aus der Nabelschnurvene (HUVEC) und von HUVEC abstammenden EA.hy926 Zellen, mit dem pan-HDAC-Inhibitor Scriptaid führte zu einer deutlichen Abnahme der Nox4 mRNA Expression. Eine ähnliche Runterregulation der Nox4 mRNA Expression konnte mit siRNA vermittelten Knockdown von HDAC3 erzielt werden. Die Inhibition in Endothelzellen ging mit verstärkter Acetylierung von Histonen, erhöhter Zugänglichkeit des Chromatins in der Nox4 Promoterregion einher. Jedoch wurde keine signifikante Veränderung der DNA-Methylierung festgestellt. Zusätzlich zeigt diese Studie, dass c-Jun eine wichtige Rolle in der Kontrolle der Nox4 Transkription spielt. Knockdown von c-Jun mit siRNA resultierte in einer Runterregulation der Nox4 mRNA Expression. Nach der Behandlung mit Scriptaid war die Bindung von c-Jun an den Nox4 Promoter verringert und dies obwohl die Chromatinstruktur weiter geöffnet war. Zusätzlich konnte gezeigt werden, dass die Bindung der RNA-Polymerase II ebenfalls deutlich verringert war, was die reduzierte mRNA Expression von Nox4 erklären könnte. Zusammenfassend kann man sagen, dass die Inhibition von HDAC die Transkription von Nox4 in menschlichen Endothelzellen verringert, indem die Bindung von Transkriptionsfaktoren und der Polymerase an den Nox4 Promoter verringert wird. Diese geringere Bindung lässt sich am besten durch ein Modell erklären indem eine Hyperacetylierung an dem Nox4 Promoter zu einer sterischen Inhibition führt. Des Weiteren scheinen auch microRNAs eine Rolle bei dem durch HDAC-induzierten Abbau der Nox4 mRNA zu spielen, denn eine Blockierung oder ein Knockdown von DICER1 hob den Effekt von Scriptaid auf die Nox4 mRNA teilweise wieder auf

    Epigenetic control of the angiotensin-converting enzyme in endothelial cells during inflammation.

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    The angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system, which is involved in the regulation of blood pressure. Alterations in ACE expression or activity are associated with various pathological phenotypes, particularly cardiovascular diseases. In human endothelial cells, ACE was shown to be negatively regulated by tumor necrosis factor (TNF) α. To examine, whether or not, epigenetic factors were involved in ACE expression regulation, methylated DNA immunoprecipitation and RNA interference experiments directed against regulators of DNA methylation homeostasis i.e., DNA methyltransferases (DNMTs) and ten-eleven translocation methylcytosine dioxygenases (TETs), were performed. TNFα stimulation enhanced DNA methylation in two distinct regions within the ACE promoter via a mechanism linked to DNMT3a and DNMT3b, but not to DNMT1. At the same time, TET1 protein expression was downregulated. In addition, DNA methylation decreased the binding affinity of the transcription factor MYC associated factor X to the ACE promoter. In conclusion, DNA methylation determines the TNFα-dependent regulation of ACE gene transcription and thus protein expression in human endothelial cells

    The Owadów-Brzezinki Geopark : aremarkable palaeontological site made available for geotourism

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    The Owadów-Brzezinki Geopark, located in the western margin of the Holy Cross Mountains in Slawno community (Łódź Voivodeship), was established in June 2019 in close vicinity of the Owadów-Brzezinki quarry. The geopark consists of palaeontological museum, educational trail and panoramic viewing platform, located along the quarry edge. The palaeontological museum exhibits unique fossils of marine and terrestrial organisms that were excavated in the quarry during the last six years. Among the most important fossils, which can be seen there are: horseshoe crabs, crustaceans, ammonites, insects, actinopterygian fish, turtles, ichthyosaurs, crocodylomorphs and pterosaurs. In addition to the original fossils, the museum presents life-size reconstructions of animals that inhabited the local seas and islands in the Late Jurassic, and plates illustating palaeogeographical and paleoenvironmental history of this site. Thanks to many important palaeontological and palaeobiological discoveries, this geopark has great geotourist and educational potential. The geopark’s design was drawn upon similar palaeontological museums such as the Jura Museum Eichstätt in the Solnhofen region and the Hauff Museum in the Holzmaden in Germany
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