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Studies on Neuropsychiatric Manifestations and Genetic Factors in Systemic Lupus Erythematosus

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease encompassing a wide range of symptoms that can emanate from pathology in virtually any organ system. Severe SLE includes involvement of the central nervous system and kidneys. One of the hallmarks of the disease is a multitude of autoantibodies, indicating a breakdown in self tolerance. The corresponding antigens have been fou

Modelling antibody orientation at bacterial surfaces

Varför gör vissa bakterier oss sjuka men inte andra? Hur kommer det sig att vissa bakterier lyckas överleva och infektera särskilda delar av kroppen men väldigt sällan andra? Bakterier och människor har evolverat länge tillsammans och har därmed lyckats utveckla specifika angrepps och försvarsmekanismer mot varandra. Det är känt sedan tidigare att några bakterier uttrycker proteiner med förmågan Bacteria and humans have co-evolved since their common existence. They have thereby developed very specific defence and target mechanisms against one another. Understanding the complex biomolecular processes behind these interactions can be of great use for developing treatments against bacterial diseases. The aim of this thesis project was to verify, and introduce a model for understanding, the i

The molecular basis of human igg-mediated enhancement of C4b-binding protein recruitment to group a streptococcus

Streptococcus pyogenes infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice.

Redox chemistry of a dimanganese(II,III) complex with an unsymmetric ligand: Water binding, deprotonation and accumulative light-induced oxidation

A dinuclear manganese complex {[(Mn2L)-L-II,IIII(mu-OAc)(2)]-ClO4} has been synthesised, where L is the dianion of 2-{[bis-(pyrid-2-ylmethyl)amino]methyl}-6-{[(3,5-di-tert-butyl-2- hydroxybenzyl)(pyrid-2-ylmethyl)amino]methyl)-4-methylphenol, an unsymmetric binucleating ligand with two coordinating phenol groups. The two manganese ions, with a Mn-Mn distance of 3.498 angstrom, are bridged by the t

Treatment Preferences for Acute Allergic Reactions : A Discrete Choice Experiment

Background: Timely treatment of acute allergic reactions (AARs) is important to minimize reaction severity. Corticosteroid tablets dissolved in water are commonly used in mainstay treatment. A new oral film that dissolves on the tongue provides a faster and less cumbersome alternative to tablets for corticosteroid administration during AARs. This study evaluated patients' preferences for attribute

Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest

BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome p

Countercurrent Distribution of Lymphocytes from Human Peripheral Blood in an Aqueous Two-Phase System : I. Separation into Subsets of Lymphocytes Bearing Distinctive Markers’

Lymphocytes from human peripheral blood have been separated by countercurrent distribution in a charged aqueous two-phase system composed of Dextran T 500 and polyethylene glycol 6000 with a cell yield of 59–88% and viability above 90%. A highly reproducible partition pattern was seen with four distinct peaks. Lymphocytes with surface membrane immunoglobulin (SmIg) were located in the first part o

Redox control of exocytosis - Regulatory role of NADPH, thioredoxin, and glutaredoxin

Cellular redox state is an important metabolic variable, influencing many aspects of cell function like growth, apoptosis, and reductive biosynthesis. In this report, we identify NADPH as a candidate signaling molecule for exocytosis in neuroendocrine cells. In pancreatic beta-cells, glucose acutely raised the NADPH-to-NADP(+) ratio and stimulated insulin release in parallel. Furthermore, intracel

Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures

Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We

Purification of streptococcal protein G expressed by Escherichia coli by high performance liquid affinity chromatography using immobilized immunoglobulin G and albumin

A one-step HPLC method was developed for the purification of protein G, a cell wall molecule from group C and G streptococci with immunoglobulin G- and albumin-binding properties. Lysed Escherichia coli bacteria infected with lambda-phages containing the protein G gene from group G streptococci were used as a starting material for the preparations. The lysate was applied to a column with immobiliz

Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis

To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. We devised a mouse model of allergen-induced allergic cystitis that is assoc

Comparison of Surface Properties of Human IgA, IgE, IgG and IgM Antibodies with Identical and Different Specificities

In this paper, the authors report the use of liquid-liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two-phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as tha

Antibody-dependent allostery of the M1 protein

Den förrädiska antikroppen Streptokocker är en lömsk bakterie som har många olika sätt att ta sig runt vårt immunförsvar. Den kan låtsas vara en del av vår kropp genom att klä sig själv i en proteinkapsel som är väldigt likt ett mänskligt protein, bryta ned våra celler med hjälp av utsöndrade gifter och använda vårt immunförsvar mot oss genom att binda antikroppar till sig själv. En virulensfaktoThe Group A streptococcus (GAS) (Streptococcus pyogenes) is a significant human pathogen known for causing a diverse range of diseases, spanning from mild diseases such as pharyngitis to life-threatening diseases such as necrotizing fasciitis. Its virulence comes from a plethora of immune evasion mechanisms, but the M protein with its hypervariable region and ability to bind human proteins, stands

Impact of site-specific conjugation strategies on the pharmacokinetics of antibody conjugated radiotherapeutics

Antibody radionuclide conjugates are an emerging modality for targeted imaging and potent therapy of disseminated disease. Coupling of radionuclides to monoclonal antibodies (mAbs) is typically achieved by applying non-site-specific labelling techniques. With the ambition of reducing variability, increasing labelling efficacy and stability, several site-specific conjugation strategies have been de

Från förening till företag - Sportslig kontra ekonomisk framgång

Syftet med uppsatsen är att undersöka vad framgång är i dagens skandinaviska elitfotbollsklubbar och vilka strategier som är användbara för att uppnå denna. Uppsatsen ämnar således belysa och klargöra de viktigaste aspekterna i en lyckad strategi inom en modern skandinavisk fotbollsklubb. Med denna kunskap har vi för avsikt att återge en bild över hur en elitfotbollsklubb strategiskt bör organiser

The derivation of first- and second-order backpropagation methods for fully-connected and convolutional neural networks

We introduce rigorous theory for deriving first and second order backpropagation methods for Deep Neural Networks (DNN) whilst satisfying existing theory in DNN optimization. We begin by formally defining a neural network with its respective components and state the first and second order chain rule with respect to its partial derivatives. The partial derivatives in the chain rule formula are rela