603 research outputs found

    Validation of aero-hydro-servo-elastic load and motion simulations in BHawC/OrcaFlex for the Hywind Scotland floating offshore wind farm

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    Klimaendringer, som et resultat av global oppvarming, krever en energiovergang: reduksjon av klimagassutslipp fra fossilt brensel og en radikal innovasjon av det globale energisystemet for å gå videre. Offshore vind er en viktig kilde til ren, fornybar energi, og den spiller en nøkkelrolle i overgangen. 80% av den verdensomspennende offshore vinden skal produseres på steder i dypt vann. her kreves flytende fundamenter, som til dags dato er langt dyrere enn deres bunnfaste kolleger. For å redusere kostnadene for flytende vindkraft er pålitelige, detaljerte spådommer om systemets belastninger og bevegelsesrespons avgjørende. Flytende offshore vindturbinkonstruksjoner er designet med 'aero-hydro-servo-elastisk' programvarekoder som simulerer den dynamiske responsen til et flytende havvindmølle-system til offshore-miljøet. Forutsigbar nøyaktighet kan forbedres ved å sammenligne simuleringsresultater fra en modell av et kjent system mot målinger hentet fra det virkelige verden, en såkalt modellvalidering. En lovende topp moderne aero-hydro-servo-elastisk programvarekode er BHawC / OrcaFlex, utviklet av Siemens Gamesa Renewable Energy (SGRE). På grunn av nyheten har validering av koden imidlertid bare blitt utført i begrenset grad, noe som gir usikkerhet rundt tolkningen av simuleringsresultater. Hensikten med denne MSc. avhandlingsprosjektet er å validere ytelsen til BHawC / OrcaFlex ved å sammenligne simulerte belastnings- og bevegelsesresultater med målinger på en reell flytende turbin fra Hywind Scotland flytende havvindpark (Hywind). Måledata og en beskrivelse av 'as-bygget' systemet ble gjort tilgjengelig av vindparkens eier Equinor ASA. For å etablere et oppnåelig nivå av modelleringsnøyaktighet og forutsigbar verdi av BHawC / OrcaFlex, ble koden bekreftet mot en annen aero-hydro-servo-elastisk programvarekode: OrcaFlex, ved å sette opp en lignende modell av Hywind-systemet i begge kodene. Begrenset informasjon er tilgjengelig om ytelsen til OrcaFlex i flytende vindbelastning og bevegelsesforutsigelser. Derfor ble det på sin side bekreftet mot et bredt spekter av bransjestandard aero-servo-hydroelastisk programvarekoder, ved bruk av et modellert system som lignet Hywind-turbinen og lastesaker som steg for steg økte i kompleksitet, for å videreføre isolere årsaker til avvik mellom modellene. OrcaFlex-spådommer samsvarte veldig godt med alle belastningssaker. Hovedforskjellene ble tilskrevet ulik modellerte ytterligere lineær hydrodynamisk demping, ettersom den offisielle dempningsresepten resulterte i prediksjonsfeil. I BHawC / OrcaFlex-verifiseringen mot OrcaFlex ble begge modellene utsatt for flere belastningstilfeller som steg for steg økte i kompleksitet, for ytterligere å isolere årsakene til avvik mellom modellene. Simuleringsresultater fra å kjøre begge modellene så ut til å være tilnærmet identiske, selv om det ble observert noe avvik på grunn av den forenklede aero-servo-elastiske OrcaFlex-koden. Den endelige valideringen av BHawC / OrcaFlex til fullskala Hywind-målinger blir utført ved undervurderte, rangerte og over utskårne vindhastigheter med fleretningsbølge og strømkomponenter. Generelt syntes BHawC / OrcaFlex bevegelsesfrekvensdomenes forutsigelser å svare til de faktiske Hywind-målingene. De fleste fenomener i lavfrekvens-, bølgefrekvens- og høyfrekvensområdet ble fanget opp av simuleringene. Imidlertid ble det observert store feil i spenningsspådommene for gjennomsnittlig bølge-, svai- og bridslinjespenning. De fleste avvikene ble funnet stammer fra feil i modelloppsettet, f.eks. mangel på hydrodynamisk demping, forenklinger i bølgemodellen eller feil i fortøyningssystemoppsettet. Tuning av fortøyningssystemet viste forbedring av resultatene, men ytterligere forbedringer kunne gjøres. Flere følsomhetsstudier ble lagt til på parametere, for eksempel hydrodynamisk drag, tårndemping og fortøyning. Dette viste overprediksjon av bølgen / svaien, og rulle / stigningsfrekvensresponsene kan dempes ved både ytterligere lineær og viskøs hydrodynamisk demping. Hovedanbefalingene for videre forskning er å analysere feil identifisert i modelloppsettet ytterligere. I tillegg skal noen, men likevel uforklarlige fenomener som ikke fanges opp av BHawC / OrcaFlex i dagens modell, tas opp. Til slutt kan utviklingen av en standardisert tilnærming for å relatere modellvalideringsstudier innen flytende vind til kostnadsforbedringer ytterligere kvantifisere verdien av fremtidige sammenligningsstudier.Climate change, as a result from global warming, requires an energy transition: the reduction of greenhouse gas emissions from fossil fuels and a radical innovation of the global energy system to proceed apace. Offshore wind is an important source of clean, renewable energy, and it plays a key role in the transition. 80% of the worldwide offshore wind is to be produced on locations in deep waters; here floating foundations are required, that to date are far more expensive than their bottom-fixed counterparts. To reduce costs of floating wind energy, reliable, detailed predictions of the system’s loads and motion response are crucial. Floating offshore wind turbine structures are designed using ’aero-hydro-servo-elastic’ software codes that simulate the dynamic response of a floating offshore wind turbine system to the offshore environment. Predictive accuracy can be improved by comparing simulation results from a model of a known system against measurements taken from the real-world system, a so-called model validation. One promising state-of-the-art aero-hydro-servo-elastic software code is BHawC/OrcaFlex, developed by Siemens Gamesa Renewable Energy (SGRE). Due to its novelty, however, validation of the code has only been carried out to a limited extend, giving rise to uncertainty about the interpretation of simulation results. The purpose of this MSc. thesis project is to validate the performance of BHawC/OrcaFlex by comparing its simulated load and motion results to measurements on a real-world floating turbine from the Hywind Scotland floating offshore wind farm (Hywind). Measurement data and a description of the ’as-built’ system were made available by the wind farm owner Equinor ASA. In order to establish an achievable level of modelling accuracy and predictive value of BHawC/OrcaFlex, the code was verified against another aero-hydro-servo-elastic software code: OrcaFlex, by setting up a similar model of the Hywind system in both codes. Limited information is available on the performance of OrcaFlex in floating wind load and motion predictions. Therefore, it was in turn verified against a wide range of industry-standard aero-servo-hydro-elastic software codes, using a modeled system that closely resembled the Hywind turbine and load cases that step-by-step increased in complexity, to further isolate causes of discrepancies between the models. OrcaFlex predictions matched very well across all load cases. The main differences were attributed to differently modeled additional linear hydrodynamic damping, as the official damping prescription resulted in prediction errors. In the BHawC/OrcaFlex verification against OrcaFlex, both models were subjected to multiple load cases that step-by-step increased in complexity, to further isolate causes of discrepancies between the models. Simulation results from running both models appeared to be nearly identical, though some discrepancy was observed from due to the simplified aero-servo-elastic OrcaFlex code. The final validation of BHawC/OrcaFlex to full-scale Hywind measurements is performed at below-rated, rated and above cut-out wind speeds with multi-directional wave and current components. In general, BHawC/OrcaFlex motion frequency domain predictions appeared to correspond well to the actual Hywind measurements. Most phenomena in the low-frequency, wave-frequency and high-frequency region were captured by the simulations. However, large errors were observed in the mean surge, sway and bridle line tensions predictions. Most discrepancies were found originating from errors in the model set-up, e.g. lack of hydrodynamic damping, simplifications in the wave model or errors in the mooring system set-up. Tuning of the mooring system showed improvement of the results, but further improvements could be made. Several sensitivity studies were added on parameters, such as hydrodynamic drag, tower damping and mooring drag. This showed overprediction of the surge/sway and roll/pitch frequency responses can be mitigated by both additional linear and viscous hydrodynamic damping. The main recommendations for further research are to further analyse errors identified in the model set-up. In addition, some yet unexplained phenomena that are not captured by BHawC/OrcaFlex in the current model, are to be addressed. Finally, a the development of a standardized approach to relate model validation studies in the field of floating wind to cost improvements could further quantify the value of future comparison studies

    Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

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    BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

    Household dysfunction and child development: Do financial resources matter?

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    Children who experience household dysfunction often report more developmental problems and lower educational attainment. A question, however, is whether these lower outcomes are caused by the household dysfunction itself, or by other (pre-existing) factors, such as growing up in poverty. Based on the extended family stress model, we derived hypotheses on the consequences of household dysfunction for child development. Furthermore, we considered the mediating and moderating role of parents’ financial resources in the impact of household dysfunction on children's development. We studied these relationships while rigorously accounting for differential selection into experiencing household dysfunction using data from the British Millennium Cohort Study and employing descriptive and fixed-effects analyses. We found that children who experienced household dysfunction after age 5 already had more behavioural problems prior to these experiences. This underscores the importance of accounting for differential selection into experiencing household dysfunction. We also found that household dysfunction beginning after age 5 led to more behavioural problems but did not impact children's verbal ability. Parents’ financial resources declined after household dysfunction, particularly among high-income households. However, we found only weak evidence of a mediating effect of financial resources, and larger declines in financial resources did not translate into larger consequences of household dysfunction among children from high-income households. Financial resources thus mainly seemed to play an important role for selection into experiencing household dysfunction

    The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery

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    The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease

    Long non-coding RNAs and cancer: a new frontier of translational research?

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    Author manuscriptTiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer.RS is supported as a fellow of the TALENTS Programme (7th R&D Framework Programme, Specific Programme: PEOPLE—Marie Curie Actions—COFUND). MIA is supported as a PhD fellow of the FCT (Fundação para a Ciência e Tecnologia), Portugal. GAC is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, as a research scholar by The University of Texas System Regents, and by the Chronic Lymphocytic Leukemia Global Research Foundation. Work in GAC’s laboratory is supported in part by the NIH/ NCI (CA135444); a Department of Defense Breast Cancer Idea Award; Developmental Research Awards from the Breast Cancer, Ovarian Cancer, Brain Cancer, Multiple Myeloma and Leukemia Specialized Programs of Research Excellence (SPORE) grants from the National Institutes of Health; a 2009 Seena Magowitz–Pancreatic Cancer Action Network AACR Pilot Grant; the Laura and John Arnold Foundation and the RGK Foundation

    E-cadherin and Cytokeratin Subtype Profiling in Effusion Cytology

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    Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic anti-gen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20- expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others

    Solid stress facilitates spheroid formation: potential involvement of hyaluronan

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    When neoplastic cells grow in confined spaces in vivo, they exert a finite force on the surrounding tissue resulting in the generation of solid stress. By growing multicellular spheroids in agarose gels of defined mechanical properties, we have recently shown that solid stress inhibits the growth of spheroids and that this growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid stress facilitates the formation of spheroids in the highly metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as spheroids in free suspension. The maximum size and the growth rate of the resulting spheroids decreased with increasing stress. Relieving solid stress by enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in 8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as spheroids in free suspension as well as in the gels, maintained their spheroidal morphology even after stress removal. Histological examination revealed that most cells in AT2.1 spheroids are in close apposition whereas a regular matrix separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan binding protein revealed that the matrix between AT3.1 cells in agarose contained hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free suspension. Hyaluronan was found to be present in both free suspensions and agarose gel spheroids of AT2.1. We suggest that cell–cell adhesion may be adequate for spheroid formation, whereas solid stress may be required to form spheroids when cell–matrix adhesion is predominant. These findings have significant implications for tumour growth, invasion and metastasis

    Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer

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    Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status

    The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression

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    <p>Abstract</p> <p>Background</p> <p>There is no biological or epidemiological data on the association between <it>NOS3 </it>promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of <it>NOS3 </it>gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.</p> <p>Methods</p> <p>This study aimed evaluating the <it>NOS3 </it>promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with <it>NOS3 </it>expression levels through semi-quantitative RT-PCR, and with <it>PCA</it>3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH.</p> <p>Results</p> <p>Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the <it>NOS3 </it>gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). <it>NOS3 </it>gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in <it>NOS3 </it>levels favored by the incorporation of each C allele. <it>NOS3 </it>levels higher than 80% of the constitutive gene expression level (<it>B2M</it>) presented a 4-fold increase in PCa occurrence.</p> <p>Conclusion</p> <p>The -786T>C polymorphism was the most important promoter alteration of the <it>NOS3 </it>gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of <it>NOS3 </it>transcripts. The <it>NOS3 </it>transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the <it>PCA3 </it>marker for molecular staging of the prostate cancer.</p
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