Numerical simulation of neoclassical currents, parallel viscosity, and radial current balance in tokamak plasmas

One of the principal problems en route to a fusion reactor is that of insufficient plasma confinement, which has lead to both theoretical and experimental research into transport processes in the parameter range relevant for fusion energy production. The neoclassical theory of tokamak transport is well-established unlike the theory of turbulence driven anomalous transport in which extensive progress has been made during last few years. So far, anomalous transport has been dominant in experiments, but transport may be reduced to the neoclassical level in advanced tokamak scenarios. This thesis reports a numerical study of neoclassical fluxes, parallel viscosity, and neoclassical radial current balance in tokamaks. Neoclassical parallel viscosity and particle fluxes are simulated over a wide range of collisionalities, using the fully kinetic five-dimensional neoclassical orbit-following Monte Carlo code ASCOT. The qualitative behavior of parallel viscosity derived in earlier analytic models is shown to be incorrect for high poloidal Mach numbers. This is because the poloidal dependence of density was neglected. However, in high Mach number regime, it is the convection and compression terms, rather than the parallel viscosity term, that are shown to dominate the momentum balance. For fluxes, a reasonable agreement between numerical and analytical results is found in the collisional parameter regime. Neoclassical particle fluxes are additionally studied in the banana regime using the three-dimensional Fokker-Planck code DEPORA, which solves the drift-kinetic equation with finite differencing. Limitations of the small inverse aspect ratio approximation adopted in the analytic theory are addressed. Assuming that the anomalous transport is ambipolar, the radial electric field and its shear at the tokamak plasma edge can be solved from the neoclassical radial current balance. This is performed both for JET and ASDEX Upgrade tokamaks using the ASCOT code. It is shown that shear high enough for turbulence suppression can be driven at the Low (L) to High (H) transition conditions without taking into account anomalous processes. In agreement with experiments, simulations indicate a higher threshold temperature for the L–H transition in JET than in ASDEX Upgrade. The parametric dependence of the shear on temperature, density, and magnetic field, however, is similar for both devices. In agreement with some theoretical models and experimental observations, the results also suggest that the critical shear for strong turbulence suppression in JET should be lower than in ASDEX Upgrade.reviewe

Homogeneous Assays for Simplified Screening of HLA-conferred Genetic Disease Risk

The increasing incidence of type 1 diabetes has led researchers on a quest to find the reason behind this phenomenon. The rate of increase is too great to be caused simply by changes in the genetic component, and many environmental factors are under investigation for their possible contribution. These studies require, however, the participation of those individuals most likely to develop the disease, and the approach chosen by many is to screen vast populations to find persons with increased genetic risk factors. The participating individuals are then followed for signs of disease development, and their exposure to suspected environmental factors is studied. The main purpose of this study was to find a suitable tool for easy and inexpensive screening of certain genetic risk markers for type 1 diabetes. The method should be applicable to using whole blood dried on sample collection cards as sample material, since the shipping and storage of samples in this format is preferred. However, the screening of vast sample libraries of extracted genomic DNA should also be possible, if such a need should arise, for example, when studying the effect of newly discovered genetic risk markers. The method developed in this study is based on homogeneous assay chemistry and an asymmetrical polymerase chain reaction (PCR). The generated singlestranded PCR product is probed by lanthanide-labelled, LNA (locked nucleic acid)-spiked, short oligonucleotides with exact complementary sequences. In the case of a perfect match, the probe is hybridised to the product. However, if even a single nucleotide difference occurs, the probe is bound instead of the PCR product to a complementary quencher-oligonucleotide labelled with a dabcyl-moiety, causing the signal of the lanthanide label to be quenched. The method was applied to the screening of the well-known type 1 diabetes risk alleles of the HLA-DQB1 gene. The method was shown to be suitable as an initial screening step including thousands of samples in the scheme used in the TEDDY (The Environmental Determinants of Diabetes in the Young) study to identify those individuals at increased genetic risk. The method was further developed into dry-reagent form to allow an even simpler approach to screening. The reagents needed in the assay were in dry format in the reaction vessel, and performing the assay required only the addition of the sample and, if necessary, water to rehydrate the reagents. This allows the assay to be successfully executed even by a person with minimal laboratory experience.Siirretty Doriast

Studies on Intrachain Conjugation, Hybridization and Invasion of Oligonucleotides

Siirretty Doriast

New biomarkers in glioma. PET/CT imaging and the prognostic value of somatostatin receptor subtype 2

Gliomas are brain tumors with dismal prognoses. They are classified based on histology and molecular biomarkers that guide therapeutic decision-making. Somatostatin receptor subtype 2- (SSTR2) targeted radionuclide therapy has been suggested as a novel treatment approach for gliomas. However, SSTR2 expression in different glioma entities is still controversial. Therefore, a method is needed for in vivo detection of SSTR2 in gliomas, which would help in the selection of patients for radionuclide therapy. Aims of this doctoral thesis were 1) to study the potential of positron emission tomography/computed tomography (PET/CT) to detect SSTR2 in gliomas in vivo, which would benefit the planning and follow-up of SSTR2-targeted radionuclide therapy, 2) to characterize SSTR2 expression in gliomas and explore its impact on survival, and 3) to evaluate serum glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) as circulating biomarkers. First, animal glioma models were studied for SSTR2 expression with PET/CT, autoradiography, and immunohistochemistry. Secondly, a prospective clinical study was conducted to examine the value of SSTR2 PET/CT and serum GFAP and EGFR in 27 patients with malignant glioma. Thirdly, SSTR2 expression and its impact on survival was retrospectively evaluated in 184 patients with glioma. SSTR2 expression was detected in experimental gliomas, but the value of SSTR2-targeted PET/CT was limited. Also, in patients with malignant glioma, PET/CT could not predict SSTR2 expression in tumor tissue. In contrast, SSTR2 expression associated with oligodendrogliomas and improved prognoses, which was confirmed in the retrospective setup. Serum GFAP correlated with glioblastomas and tumor burden, whereas circulating EGFR was not related to tumor EGFR expression. In conclusion, SSTR2 and serum GFAP are potential new biomarkers with diagnostic, prognostic, and/or therapeutic value. SSTR2 PET/CT has limited value in selecting glioma patients for radionuclide therapy.Gliooman uudet biomarkkerit – somatostatiinireseptorien PET/TT -kuvantaminen ja vaikutus ennusteeseen Glioomat ovat pahanlaatuisia aivokasvaimia, joilla on taipumus uusiutua nopeasti. Kudosnäytteistä määritettävät molekyylipatologiset merkkiaineet ovat tärkeitä glioomien luokittelussa sekä ennusteen ja hoitovasteen arvioinnissa. Huonon ennusteen vuoksi glioomien uusia hoitomenetelmiä tutkitaan intensiivisesti. Tämän väitöskirjatyön tarkoituksena oli tutkia somatostatiinireseptorien (alatyyppi 2, SSTR2) ilmentymistä glioomissa sekä histologian että positroniemissiotomografia/tietokoneto-mografiakuvauksen (PET/TT) avulla. Taustalla oli ajatus SSTR2:een sitoutuvasta radiolääkkeestä, jota on ehdotettu uusiutuneiden pahanlaatuisten glioomien hoitomuodoksi. Hoidon edellytyksenä on, että kasvaimet ilmentävät SSTR2:a, johon sekä PET-merkkiaine että radiolääke pääsevät sitoutumaan. Lisäksi tavoitteena oli potilaiden verinäytteistä tutkia mahdollisia biomerkkiaineita (GFAP, glial fibrillary acidic protein sekä EGFR, epidermal growth factor receptor) glioomien luokittelua ja seurantaa varten. SSTR2:n ilmentymistä ja PET/TT-kuvantamista tutkittiin sekä kokeellisessa eläinmallissa että 27 potilaalla, jotka sairastivat pahanlaatuista glioomaa. Potilaiden verinäytteistä määritettiin lisäksi GFAP- sekä EGFR–pitoisuudet. Lopuksi SSTR2:n ilmentymistä tutkittiin retrospektiivisesti 184 glioomanäytteestä sekä ilmentymisen yhteyttä potilaan ennusteeseen. Kokeellinen gliooma ilmensi SSTR2:a, mutta PET/TT-kuvauksen hyöty tämän arvioimiseksi jäi alhaiseksi. Glioomapotilailla ei myöskään löytynyt yhteyttä kudosnäytteen SSTR2:n ilmenemisen ja PET-merkkiainekertymän välillä. Sen sijaan SSTR2:n ilmeneminen näytti liittyvän vahvasti aivokasvainten oligodendrogliaaliseen alatyyppiin sekä suotuisampaan ennusteeseen. Tämä yhteys vahvistettiin retrospektiivisessä työssä. Korkean seerumin GFAP-pitoisuuden todettiin lisäksi liittyvän aggressiivisiin glioblastoomiin sekä kasvaimen kokoon. Seerumin EGFR-pitoisuus sen sijaan ei liittynyt kasvainkudoksesta tehtyihin EGFR-määrityksiin. Tulokset viittaavat siihen, että SSTR2 ja seerumin GFAP voivat toimia sekä luokittelevina että ennusteellisina biomerkkiaineina glioomien hoidossa ja/tai seurannassa. PET/TT-kuvantamisella on kuitenkin vähäinen merkitys radiolääkehoidon arvioinnissa.Siirretty Doriast

A Review of IFC Standardization – Interoperability Through Complementary Development Approaches

The Industry Foundation Classes (IFC) data model has been in development by an industry consortium since 1994; during this time the industry context, standardization organization, resource availability, and technology development have exposed the standardization process to a dynamic environment. While the overarching mission of IFC standardization has always been to provide interoperability between AEC/FM software applications and actors, both the goals and the views on how to best achieve those goals have changed throghout the years. Despite the fact that IFC has enjoyed sustained professional and scholarly interest throughout its development, reflective socio-technical studies on the subject are largely non-existent. This study reviews the major shifts in the development process of the IFC standard from its origins in the early 1990s up to 2011, splitting the timeline into four distinct phases. A finding of the review is that the IFC standardization process has utilized complementary minimalist and structuralist approaches for different phases of the standardization process - balancing exhaustive structuralism and implementable minimalism. The concepts behind Model View Definitions (MVD), Information Delivery Manuals (IDM), and the International Framework for Dictionaries (IFD) were not documented from the start and only became relevant as standardization progressed, with each of the components contributing minimalism to a structurally constructed data model