985 resultados para TB diagnostics


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Metal-ion-mediated base-pairing of nucleic acids has attracted considerable attention during the past decade, since it offers means to expand the genetic code by artificial base-pairs, to create predesigned molecular architecture by metal-ion-mediated inter- or intra-strand cross-links, or to convert double stranded DNA to a nano-scale wire. Such applications largely depend on the presence of a modified nucleobase in both strands engaged in the duplex formation. Hybridization of metal-ion-binding oligonucleotide analogs with natural nucleic acid sequences has received much less attention in spite of obvious applications. While the natural oligonucleotides hybridize with high selectivity, their affinity for complementary sequences is inadequate for a number of applications. In the case of DNA, for example, more than 10 consecutive Watson-Crick base pairs are required for a stable duplex at room temperature, making targeting of sequences shorter than this challenging. For example, many types of cancer exhibit distinctive profiles of oncogenic miRNA, the diagnostics of which is, however, difficult owing to the presence of only short single stranded loop structures. Metallo-oligonucleotides, with their superior affinity towards their natural complements, would offer a way to overcome the low stability of short duplexes. In this study a number of metal-ion-binding surrogate nucleosides were prepared and their interaction with nucleoside 5´-monophosphates (NMPs) has been investigated by 1H NMR spectroscopy. To find metal ion complexes that could discriminate between natural nucleobases upon double helix formation, glycol nucleic acid (GNA) sequences carrying a PdII ion with vacant coordination sites at a predetermined position were synthesized and their affinity to complementary as well as mismatched counterparts quantified by UV-melting measurements.

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Camilla Pelo Collagen Binding Integrins and Cancer Testis Antigens in Prostate Cancer and Melanoma Department of Biochemistry, MediCity Research Laboratory, University of Turku, Finland Annales Universitatis Turkuensis, Painosalama Oy, Turku, Finland 2016 ABSTRACT Prostate cancer is the second most common cancer in men worldwide. The incidence of melanoma, in turn, is increasing faster than any other cancer incidences. In Finland, more than 5000 prostate cancer and 1200 new melanoma cases are diagnosed each year. One approach to further understand the cellular processes involved in prostate cancer and melanoma is to gain better knowledge about alterations in gene expression and their potential impact on the progression of the diseases. This thesis is focused on expression studies in two gene families; integrins and cancer testis antigens (CT antigens), in human prostate adenocarcinoma and advanced human melanoma. Integrins are heterodimeric transmembrane receptors which regulate many important cellular processes such as cell proliferation, migration and survival. CT antigens are frequently expressed in different types of cancers, but are only expressed in testis in healthy individuals. CT antigens are also highly immunogenic proteins. Due to the properties mentioned above, integrins and CT antigens can function as target molecules for the development of cancer diagnostics and drugs. One of the main purposes of this thesis was to study the expression of the four collagen binding integrins α1β1, α2β1, α10β1, α11β1 and the cancer testis antigen 16 (CT16) in cancer cell lines and human tissues of prostate cancer and metastatic melanoma. Additional aims included studies on the biological role of CT16 and the abundance of CT16 in sera of advanced melanoma patients. The prognostic and diagnostic significance of CT16 and the collagen binding integrins were also evaluated. Expression studies on collagen binding integrins and the CT antigen CT16 in melanoma and prostate cancer were limited and the biological role of CT16 was unknown. In this thesis, the expression levels of α2β1 and α11β1 were found to be significantly altered in prostate cancer tissues. Integrin α2β1 decreased gradually during disease progression while α11 was elevated in prostate carcinoma compared to healthy tissues. In advanced melanoma, enhanced levels of α2 were associated with a significant shorter overall survival in advanced melanoma. In this thesis, CT16 was identified as a frequently expressed melanoma CT antigen with an anti-apoptotic function. To conclude, this thesis presents α2β1 and CT16, as potential and promising biomarkers for advanced melanoma. This thesis reports also the first functional study of CT16. Keywords: Collagen binding integrins, α1β1, α2β1, α10β1, α11β1, Cancer Testis antigens, CT16, melanoma, prostate cancer, expression

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Tässä tutkimuksessa selvitettiin, miten suorituskyvyn johtamista ja mittaamista käytännössä toteutettiin suuressa tutkimus- ja tuotekehitystoimintaa Suomessa harjoittavassa elintarvikealan yrityksessä. Tutkimuksessa kartoitettiin tärkeimpiä suorituskykyyn vaikuttavia tekijöitä suorituskyvyn johtamisen ja mittaamisen näkökulmasta. Tutkimuksen tavoitteena oli saada kooste suosituksista tutkimus- ja tuotekehitystoiminnan suorituskyvyn johtamisen ja mittaamisen kehittämiseksi. Tutkimuksen laajuus rajattiin neljään case-yritykseen. Tutkimuksessa tehtiin empiirinen puolistrukturoitu kyselytutkimus, strukturoidut haastattelut sekä tulosten arviointi. Tutkimusote oli lähinnä toiminta-analyyttinen, koska tutkimuksessa käsiteltiin organisaation toimintaa, johtamista, ongelmanratkaisua, päätöksentekoprosesseja sekä kehitys- ja muutosprosesseja. Tutkimustulosten perusteella suorituskyvyn johtamista ja mittaamista case-yrityksissä toteutettiin BSC:n yleisten näkökulmien mukaisesti. Tutkimus- ja tuotekehitystoiminnan mittauksen tavoitteet poikkesivat toisistaan niiden toiminnan luonteesta johtuen. Tutkimustoiminnassa suorituskyvyn mittauksen tavoitteet painottuivat lähinnä innovatiivisuuteen, oppimiseen ja motivointiin. Tuotekehitystoiminnassa mittauksen tavoitteet olivat enemmän diagnostisia. Tuotekehitystoiminnassa tavoitteena olivat projektien seurantaan, toiminnan tulostenarviointiin, talouteen sekä koordinaatioon ja kommunikointiin liittyvät tekijät. Tutkimustulosten perusteella puutteita havaittiin suorituskyvyn viestinnän riittävyydessä ja vaikuttavuudessa, mittaustiedon hyödynnettävyydessä, aineettoman pääoman mittauksessa, projektien arviointikriteerien viestinnässä, prosessien selkeydessä ja toimivuudessa, projektiosaamisessa, suorituskyvyn mittauksessa, vaikutusmahdollisuuksissa, johtamisessa ja esimiestyössä.

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Diabetic retinopathy, age-related macular degeneration and glaucoma are the leading causes of blindness worldwide. Automatic methods for diagnosis exist, but their performance is limited by the quality of the data. Spectral retinal images provide a significantly better representation of the colour information than common grayscale or red-green-blue retinal imaging, having the potential to improve the performance of automatic diagnosis methods. This work studies the image processing techniques required for composing spectral retinal images with accurate reflection spectra, including wavelength channel image registration, spectral and spatial calibration, illumination correction, and the estimation of depth information from image disparities. The composition of a spectral retinal image database of patients with diabetic retinopathy is described. The database includes gold standards for a number of pathologies and retinal structures, marked by two expert ophthalmologists. The diagnostic applications of the reflectance spectra are studied using supervised classifiers for lesion detection. In addition, inversion of a model of light transport is used to estimate histological parameters from the reflectance spectra. Experimental results suggest that the methods for composing, calibrating and postprocessing spectral images presented in this work can be used to improve the quality of the spectral data. The experiments on the direct and indirect use of the data show the diagnostic potential of spectral retinal data over standard retinal images. The use of spectral data could improve automatic and semi-automated diagnostics for the screening of retinal diseases, for the quantitative detection of retinal changes for follow-up, clinically relevant end-points for clinical studies and development of new therapeutic modalities.

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1897 (TB)-1906.

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1907 (TB)-1924.