484 research outputs found

    BRCA1-null versus BRCA1 hypermethylated TNBC

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    Uploaded data include: 1. Frequencies of copy number gain and loss, LOH, and copy neutral LOH for 57 BRCA1 hypermethylated and 52 BRCA1-null tumors. 2. RNAseq data for 27 ER- and PR-negative BRCA1 germline cases originally reported by Jönsson et al. (PMID=22706203) as GSE25307. RNAseq data was generated and summarized to FPKM as described in Brueffer et al. (JCO Precision Oncology, 1-18 (2018).)

    RNA Sequencing-Based Single Sample Predictors of Molecular Subtype and Risk of Recurrence for Clinical Assessment of Early-Stage Breast Cancer

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    Gene expression data and associated supplementary files from RNAseq of breast cancer samples from Staaf et al. npj Breast Cancer 2022 (source reference below). Library preparation for mRNA-sequencing was done by a stranded dUTP mRNA protocol or by Illumina stranded TruSeq mRNA protocol. Expression data (Fragments Per Kilobase per Million reads, FPKM) was generated by an analysis pipeline utilizing Hisat/StringTie with GRCh38 human genome primary assembly and GENCODE Release 27 transcripts/genes. Gene expression data is summarized on GENCODE gene identifier. Gene and transcript definitions and gene annotations are from GENCODE Release 27.Detailed description including material and methods for RNAseq, Hisat/StringTie analysis pipeline, and the development of the Single Sample Predictor (SSP) models for Breast Cancer is available in Staaf et al. npj Breast Cancer 2022 (source reference below).The developed SSP models are available as an R package available at GitHub (reference below)

    Childhood Obesity and Islet Function

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    The prevalence of childhood obesity and Type 2 Diabetes Mellitus (T2DM) has increased during recent decades. T2DM is accompanied with functional changes in the islets of Langerhans, which can be identified early in the pathogenesis. The aim of this thesis was to explore how metabolic changes caused by obesity early in life relate to islet function prior to overt T2DM. To address this, Uppsala Longitudinal Study of Childhood Obesity (ULSCO) was established (paper I). Initially, the association between palmitate and insulin secretion was investigated using a translational approach with obese and lean normoglycemic juveniles and isolated human islets (paper II). Secondly, dynamics of islet-hormones insulin and glucagon, and gut-hormones glucagon like-peptide 1 (GLP-1) and glicentin (paper III) and magnetic resonance imaging of pancreatic fat fraction (PFF) (paper IV) were studied in association to glucose tolerance and beta-cell function. Finally, a novel method of analysing shape features of oral glucose tolerance test (OGTT) curves was introduced and evaluated (paper V). Obese subjects had high prevalence of prediabetes and metabolic syndrome (MetS) (paper I). In obese pre-pubertal children with elevated palmitate levels, hyperinsulinemia was observed (paper II). In contrast, obese pubertal adolescents with similar palmitate levels showed moderate insulin levels during OGTT with delayed first phase insulin response. To explore mechanisms for these variations, isolated human islets were exposed to palmitate for different time periods in vitro. After 2 days accentuated insulin response was observed. Impaired beta-cell function and apoptosis were evident after 7 days, however. Hyperglucagonemia and disturbed GLP-1 and glicentin levels were associated with obesity and glycaemic status, with fasting glicentin being predictive of prediabetes (paper III). Furthermore, PFF was increased in obese subjects and associated to MetS and visceral adipose tissue, but not to beta-cell function (paper IV). OGTT curves were converted into geometric centres, centroids, which correlated with differences in glucose tolerance (paper V). In conclusion, the islet function in obese children was associated with elevated levels of palmitate, but not pancreatic fat. Fasting palmitate and glicentin levels, as well as centroid analyses of OGTT curves, could potentially identify obese children at risk of prediabetes and subsequent T2DM

    Genomic profiling of breast cancer by microarray-based technology and bioinformatics

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    Cancer is a genetic disease that arises when a cell acquires unlimited growth potential through a series of mutational events, which target genes essential for normal cell control and maintenance. Breast cancer is one of the most frequent malignancies in women worldwide, and it is characterized by heterogeneous tumor biology, histological subtypes, variable prognosis and variable responsiveness to treatment. Breast tumors frequently harbor a vast amount of genetic alterations including point mutations, structural rearrangements, and gain or loss of genetic material. These genetic alterations are believed to be hallmarks of gene deregulation and genome instability. In breast cancer, patterns of DNA copy number alterations have been shown to be specific for subtypes of breast cancer. Furthermore, recurrent alterations can point towards genes important in breast cancer carcinogenesis and may disclose potentially novel therapeutic targets, as exemplified by the HER2 oncogene. In the current thesis, microarray platforms and data analysis algorithms have been developed for investigation of DNA copy number alterations in breast cancer. Microarray platforms based on comparative genomic hybridization (aCGH) were developed for both genome-wide and focused delineation of complex genomic aberrations in breast cancer cells. Findings from data analysis of breast cancer cells motivated further investigation of a crucial step in low-level aCGH data analysis, normalization, resulting in a normalization strategy specifically for aCGH data. These methods were combined to characterize genomic aberrations in breast tumors harboring amplification of the HER2 oncogene, pinpointing significant aberrations including both known and potentially novel therapeutic targets. Moreover, using a bottom-up discovery strategy, analysis of global gene expression profiles from 58 HER2-amplified tumors revealed three subgroups of HER2+ tumors with different clinical characteristics and outcomes. A HER2-derived prognostic predictor was constructed based on analysis of genes differentially expressed among the three subgroups. Validation of the predictor in independent breast cancer data sets proved the prognostic association in HER2-amplified breast cancer, as well as other clinically challenging breast cancer subgroups. Together, the results shed further light on the genomically complex and heterogeneous nature of HER2-amplified breast cancer that may have therapeutic implications

    Jämförande analys mellan svenska och portugisiska reklambyråer. : Saker som är bra att veta om man ska arbeta som grafisk formgivare i Sverige eller i Portugal

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    If you move from Sweden to Portugal to work as an Art Director at an Ad agency, there are certain things you ought to know. Perhaps even before you decide to move. There are a lot of things that are quite different if you compare Portugal to Sweden, not only the language, but also the design, software, working hours and much more. You have for example two month with double salary, you work till six p.m. and when it comes to maternity leave, you have 100% compensation with no taxes the first four months of every pregnancy. The tasks you have to handle as an Art Director in Portugal may, as in Sweden, be various. The difference is more how you solve your task and what the design looks like. As a Swede in Portugal the solution will probably look like a mixture between the Portuguese “expressive” and the Swedish “clean” design. This degree project discusses questions that might turn up when a Swede gets employed as an Art Director in Portugal. What will the salary be? When, in the morning, is it time to show up at the office? How many weeks of vacations are entitled? There are a lot of distinctions, but also a lot of similarities. The report is mainly based upon the author’s own experiences of the Ad agency McCann-Erickson in Lisbon. The history of McCann-Erickson starts in New York, 1930 and grew rapidly into one of the leading corporation with agencies all over the world. It is still today one of the world’s largest Ad company with clients like Coca-Cola and General Motors, and the slogan “truth well told” still lights up all their agencies after almost a century, just like a leading star

    Stijfheid en Sterkte II

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    Collegedictaat, bachelorfase in Faculteit der Werktuigbouwkunde en Maritieme Techniek van de Technische Universiteit Delft, uitgave december 1988. Inhoudsopgave: 1. Continuumtheorie, de prismatische staaf en toelaatbare spanningen 2. Vakwerkconstructies en staafmechanismen 3. Constructies met buig- en torsiestijve staven 4. Twee-dimensionale balkconstructies 5. Computerprocedures voor de analyse van constructies Bijlagen (3)Engineering MechanicsMechanical, Maritime and Materials Engineerin

    Dissertatio physica de conglaciatione: qvam, suffragante ampliss. facult. philos. in Reg. ad Auram Academia, sub praesidio mag. Johannis Browallii, scient. natur. prof. reg. & ord. Publico bonorum examini, qua par est modestia, submittit Ericus S. Backmann Jemtius. Ad d. 13. Decemb. MDCCXXXVIII, loco horisqve solitis

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    Invocatio: Divina adfulgente gratia.Dedicatio: Jonas Fahlenius, Jeremias Wallen, Petrus Klefberg, Abrahamus Bång, Olavus Flodalin, Petrus Staaf, Johannes Sundell, Simon Gunnarsson [ruots. runo].Grat.: Olaus Huss, A[ndreas] F[agerholm], Joannes P[etri] Haegermarck [ruots. runo].Arkit: 4 arkintunnuksetonta lehteä, A-B8 C6.Painovuosi nimekkeestä
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