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X-linked agammaglobulinemia (XLA) is a hereditary defect of B-cell differentiation in man caused by deficiency of Bruton tyrosine kinase (BTK). A three-dimensional model for the BTK kinase domain, based on the core structure of cAMP-dependent protein kinase, was used to interpret the structural basis for disease in eight independent point mutations in patients with XLA. As Arg-525 of BTK has been
ABSTRACT Optimal breeding of mice is very important in biomedical science today. The understanding why some strains breed better and some worse enable scientists to create better in vivo models for human diseases. The aim of this thesis was to identify and characterize new genetic regions linked to reproductive performance and autoimmune inflammation in female mice. Collagen-induced arthritis (CIA
The epithelia are the avascular layers of cells that cover the environment-exposed surfaces of the body. It appears that T cells localize to selected sites in or adjacent to epithelia via the selective expression of adhesion molecules and chemokine receptors on T cells. These bind to counter-receptors and to chemokines expressed by epithelial cells. Recently, there has been an advance in our under
The therapeutic potential of glial cell line-derived neurotrophic factor ( GDNF) for Parkinson's disease is likely to depend on sustained delivery of the appropriate amount to the target areas. Recombinant adeno-associated viral vectors ( rAAVs) expressing GDNF may be a suitable delivery system for this purpose. The aim of this study was to define a sustained level of GDNF that does not affect the
About 25% of C2-deficient homozygotes have increased susceptibility to severe bacterial infections. C2-deficient homozygotes had significantly lower serum levels of IgG2, IgG4, IgD, and Factor B, significantly higher levels of IgA and IgG3 and levels of IgG1 and IgM similar to controls. Type I ( 28 bp deletion in C2 exon 6 on the [HLA-B18, S042, DR2] haplotype or its fragments) and type II ( non-t
The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art
Human complex-forming glycoprotein, heterogeneous in charge (protein HC) has previously been isolated from urine and immunochemically shown to be present in low and high molecular weight forms in blood plasma (Tejler, L., and Grubb, A. O. (1976) Biochim. Biophys. Acta 439, 82-94). In the present work, the major low and high molecular weight forms of the protein were isolated from plasma by immunos
High-resolution precision spectroscopy provides a multitude of robust techniques for probing exoplanetary atmospheres. We present multiple VLT/ESPRESSO transit observations of the hot-Jupiter exoplanet WASP-19b with previously published but disputed atmospheric features from lowresolution studies. Through spectral synthesis and modelling of the Rossiter-McLaughlin (RM) effect we calculate stellar,
Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considera
This biomechanics study explored stride length (SL), duration (SDN), and gait ground reaction forces (GRFspeak), required coefficient of friction (RCOFpeak), joint angle (anglepeak, anglemin), angular velocities (angvelx peak), angular accelerations (angaccx peak), muscle electromyography (EMG) during the dominant leg stance phase (SP) following an exhaustive stair ascent for evacuation. Data were
Fires in road tunnels constitute complex scenarios with interactions between the fire, tunnel users and safety measures. More and more methodologies for risk analysis quantify the consequences of these scenarios with complex models. Examples for complex models are the computational fluid dynamics model Fire Dynamics Simulator (FDS) and the microscopic evacuation model FDS+Evac. However, the high c
Objective: Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. Approach and results: Using human coronary artery smooth musc
The Radial Velocity Experiment (Rave) is a magnitude-limited (9 < I < 12) spectroscopic survey of Galactic stars randomly selected in Earth's southern hemisphere. The Rave medium-resolution spectra (R ∼ 7500) cover the Ca-triplet region (8410-8795 Å). The sixth and final data release (DR6) is based on 518,387 observations of 451,783 unique stars. Rave observations were taken between 2003 April 12
Background: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation
Gene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenv
Background: The dual antiplatelet therapy (DAPT) score guides decisions on DAPT duration after coronary stenting by simultaneously predicting ischemic and bleeding risk. Objectives: This study sought to assess the performance of the DAPT score in a nationwide real-world population. Methods: The study used register data in Sweden (2006 to 2014) and followed 41,101 patients who had undergone 12 mont
The need for digital building information is increasing, both in the form of 3D city models (as geodata) and of more detailed building information models (BIM). BIM models are mainly used in the architecture, engineering and construction industry, but have recently become interesting also for municipalities. The overall aim of this paper is to study one way of dividing a building, namely the divis
The secretion of alpha 1-microglobulin by primary cultures of rat hepatocytes was found to increase upon the addition of interleukin-6 or leukemia inhibitory factor, two mediators of acute phase response. This stimulatory effect was further enhanced by dexamethasone. alpha 1-Microglobulin is synthesized as a precursor also containing bikunin, and the precursor protein is cleaved shortly before sec
In order to generate monoclonal antibodies (MAb) directed against the low molecular weight glycoprotein alpha 1-microglobulin, a BALB/c mouse was immunized with a mixture of human, guinea pig, rat and rabbit alpha 1-microglobulin homologues (multi-species immunization) and boosted several times. On day 194, the mouse splenocytes were fused to SP2/0 myeloma cells. The resulting hybridomas were scre
