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Metformin is a first-line oral agent used in the treatment of type 2 diabetes, but glycaemic response to this drug is highly variable. Understanding the genetic contribution to metformin response might increase the possibility of personalising metformin treatment. We aimed to establish the heritability of glycaemic response to metformin using the genome-wide complex trait analysis (GCTA) method.
Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG(1) carbamylation under inflammatory conditions and the effects that this m
Background: As 13-valent pneumococcal conjugate vaccine (PCV13) is introduced, children who began vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) may complete their vaccination with PCV13. This open-label phase 3 study evaluated immunogenicity and safety of PCV13 in Swedish infants and toddlers previously given 1 or 2 doses of PCV7 during infancy. Methods: Healthy infants previousl
Moraxella catarrhalis is a respiratory tract pathogen commonly causing otitis media in children and acute exacerbations in patients suffering from chronic obstructive pulmonary disease. Cartilage oligomeric matrix protein (COMP) functions as a structural component in cartilage, as well as a regulator of complement activity. Importantly, COMP is detected in resident macrophages and monocytes, alveo
The generation of toxic oligomers during the aggregation of the amyloid-beta (A beta) peptide A beta 42 into amyloid fibrils and plaques has emerged as a central feature of the onset and progression of Alzheimer's disease, but the molecular pathways that control pathological aggregation have proved challenging to identify. Here, we use a combination of kinetic studies, selective radiolabeling expe
The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apopto
Introduction During the embodiment design and detail design phase, the designer has at his disposal a set of tools and techniques that him or her through the synthesis activity: basic rules, guidelines and principles (see [1]), but in the literature there are general design processes that help the designer to organize their work (e.g. [1]), but not at a very operational level. From a previous stud
Popular Abstract in Swedish Blekinge tillhörde före freden i Roskilde 1658 Danmark. De östdanska provinserna erövrades av svenskarna och integrerades i det svenska riket. Övergångsproblematiken har i äldre forskning ofta diskuterats och analyserats med begrepp hämtade från en senare tids nationella föreställningar. Men var de motsättningar och konflikter som utvecklades i Blekinge efter övergångenThe object of this thesis is to examine the incorporation of the former Danish province of Blekinge into Sweden after the Treaty of Roskilde in 1658. This question has been analysed before but such studies have usually been coloured by the use of national ideas and notions born of a later age than the period under examination. This thesis analyses the so-called Transition Problem using theoretical
We have investigated the Raman-Auger crossover of the Mn 2p non-radiative decays in bulk MnO. For the highest kinetic energy transition in the Mn 2p3p3p decay, Raman behaviour is observed up to approximate to 3.4 eV above the resonance energy (maximum of the L-3 absorption). In the case of the 2p3p3d and 2p3d3d transitions a similar situation occurs up to approximate to 5 eV above the resonance en
The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the
Popular Abstract in Swedish Inom svensk mjölkproduktion förekommer en hög frekvens av belastningsbesvär. Vid jämförelser mellan manliga och kvinnliga mjölkare har det visat sig vara stora skillnader avseende besvärsförekomst. Kvinnorna har rapporterat högre frekvens av problem i nästan alla kroppsdelar jämfört med männen. Dessutom har andelen hand- och handledsbesvär visat sig vara anmärkningsvärdThe aims of the thesis were to investigate the prevalence of the upper extremity musculoskeletal disorders in female milkers in relation to other occupational groups; to clarify the relationship between disorders and work environment, psychosocial and life style factors; to compare in a prospective study, pain, ache and discomfort reported by a questionnaire with clinical symptoms and sign; to exa
Nanometer-scale electron devices containing three-terminal ballistic junctions are fabricated by electron-beam lithography on InP/InGaAs two-dimensional electron gas materials. Based on the intrinsic nonlinearity of the devices, frequency mixer, phase detector and RS flip-flop memory functioning at room temperature are successfully achieved. The devices have simple structure layout and small size,
Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (P13K) pathway is frequently activated in solid tumors; however, currently, no reliable test for P13K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of P13K, results in robust activation of this pathway, we developed and
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucosidase, beta, acid (GBA) gene that encodes the lysosomal enzyme glucosylceramidase (GCase). GCase deficiency leads to characteristic visceral pathology and, in some patients, lethal neurological manifestations. Here, we report the generation of mouse models with the severe neuronopathic form o
Galectin-8 is a carbohydrate-binding protein that plays a crucial role in tumor progression and metastasis, antibacterial autophagy, modulation of the immune system, and bone remodeling. The design, synthesis, and protein affinity evaluation of a set of C-3 substituted benzimidazole and quinoline d-galactal derivatives identified a d-galactal-benzimidazole hybrid as a selective ligand for the gale
The core level photoemission and near edge X-ray photoabsorption spectra of guanine in the gas phase have been measured and the results interpreted with the aid of high level ab initio calculations. Tautomers are clearly identified spectroscopically, and their relative free energies and Boltzmann populations at the temperature of the experiment (600 K) have been calculated and compared with the ex
The thesis deals with the representation of fantasy in modern film with special regards to parallel-world stories. In order to demarcate parallel worlds from other types of magical worlds in fantasy stories, the thesis contains an extensive chapter of definitions. Starting out with Todorov’s and Jackson’s well-known theories on fantasy / the fantastic, the thesis turns to other approaches allowing
Modern solid-state klystron modulators generate high-voltage, high-power pulses by discharging energy stored in a capacitor bank. Such modulators require at least one capacitor charging unit supplying the energy released in pulsing. Traditional capacitor charging structures rely on AC/DC front-end units based on passive diode rectifiers in conjunction with high-frequency resonant converters. Howev
