Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

EVALUATION OF A METHOD FOR MEASURING MIXING TIME USING NUMERICAL SIMULATION AND EXPERIMENTAL DATA

A method for measuring mixing performance in large-scale vessels is investigated. The method is evaluated experimentally in a pilotscale reactor and by using a model based on the three-dimensional calculation of the flow field. The method is based on injection of a tracer and measuring the concentration with several detectors at different locations. The mixing performance is measured as the decay rate of the difference between the concentration at the detectors and the final concentration.

The model predicts a strong dependence on injection point. The assumption of a first-order decay rate of the concentration deviation is more appropriate for some injection points.     

Introduction of lysine residues on the light chain constant domain improves the labelling properties of a recombinant Fab fragment

Europium chelates provide a non-radioactive alternative forsensitive labelling of antibodies for diagnostic immunoassays.Lysine residues at antibody surfaces are ready targets for labellingby an isothiocyanate derivative of the europium chelate (Eu³⁺).Here the labelling efficiency of a recombinant anti-human -fetoprotein(hAFP) Fab fragment has been improved by increasing its lysinecontent by protein engineering. Molecular modelling was usedto identify three light chain constant domain surface arginineresidues, R154, R187 and R210, which were mutated to lysineresidues. The mutations did not influence the affinity of thelysine-enriched Fab fragment and its labelling efficiency wasfound to be 40% higher than that of the wildtype Fab fragmentWith low degree of labelling, the affinities of the two Fabfragments were identical and comparable with that of the originalmonoclonal anti-hAFP IgG. With a higher degree of labellingthe affinities of both Fab fragments decreased more than thatof the intact IgG since more lysine residues are available forlabelling in the additional heavy chain constant domains ofthe larger molecule. Electrostatic adsorption and covalent immobilizationof the Fab fragments were characterized by BIAcore^TM and thelysine-enriched Fab fragment was found to be more efficientlyimmobilized to an activated carboxymethyl surface.     

Screening of serum samples from Wegener's granulomatosis patients using antibody microarrays

Wegener's Granulomatosis (WG) is an idiopathic granulomatosis autoimmune vasculitis that primarily affects small vessels and is associated with glomerulonephritis and pulmonary granulomatous vasculitis. Anti‐neutrophil cytoplasmic auto‐antibodies (cANCA) against proteinase‐3 are used to identify WG, but ANCA titers are not present in some patients with the localized disease. The objective of this study was to develop an antibody array to help identify protein expression patterns in serum from patients with WG as compared to normals. The arrays were tested for limits of detection, background, and cross reactivity using standard proteins. The arrays were hybridized with either normal patient serum (n = 30) or with serum samples from a population of WG patients (n = 26) that were age and sex matched. Data analysis and curve fitting of the standard dilution series calculated r² values and determined a sensitivity of <50 pg/mL for the majority of proteins. A total of 24 proteins were assessed. Several statistically significant increases (p<0.05) were seen in the expression of: angiotensin converting enzyme‐I, IFN‐γ, IL‐8, s‐ICAM‐1 and s‐VCAM in WG patients as compared to controls. Utilizing the antibody microarray technology has led to the identification of potential biomarkers of vascular injury in the serum of WG patients.     

An alternating low band-gap polyfluorene for optoelectronic devices

An alternating polyfluorene (APFO) with low band-gap segments named APFO-Green1 has been designed and synthesized for use in optoelectronic devices. The low band-gap segment consists of an electron acceptor (A), fenced by electron donors (D). This D-A-D configuration leads to a partial charge transfer in the polymer backbone, and thereby a low band-gap (1.3 eV). Results obtained from characterization of APFO-Green1 include light absorption and emission at extended wavelengths as well as high hole mobility. Furthermore, blends of the polymer with different fullerene derivatives exhibit unusually high photovoltaic performance at long wavelengths, making this type of conjugated polymers promising for plastic solar cell applications.     

Conjugated polymers with polar side chains in bulk heterojunction solar cell devices

Two polymers with polar side chains, namely poly[2,7‐(9,9‐dioctylfluorene)‐alt‐5,5‐(5',8'‐di‐2‐thienyl‐(2',3'‐bis(3''‐(2‐(2‐methoxyethoxy)ethoxy)phenyl)quinoxaline))] ( P1 ) and poly[2,7‐(9,9‐bis(2‐(2‐methoxyethoxy)ethyl)fluorene)‐alt‐5,5‐(5',8'‐di‐2‐thienyl‐(2',3'‐bis(3''‐(2‐(2‐methoxyethoxy)‐ethoxy)phenyl)quinoxaline))] ( P2 ), were synthesized for solar cell application. A series of bulk heterojunction solar cells were systematically fabricated and characterized by varying the electron‐acceptor materials, processing solvents and thickness of the active layer. The results show that P1 , with a higher molecular weight and good film‐forming properties, performed better. The best device showed an open circuit voltage of 0.87 V, a short circuit current of 6.81 mA cm^?2 and a power conversion efficiency of 2.74% with 1:4 polymer:[6,6]‐phenyl‐C71‐butyric acid methyl ester (PCBM[70]) mixture using o‐dichlorobenzene (o‐DCB) as processing solvent. P2 on the other hand showed a poorer performance with chlorobenzene as processing solvent, but a much improved performance was obtained using o‐DCB instead. Thus, an open circuit voltage of 0.80 V, short circuit current of 6.21 mA cm^?2 and an overall power conversion efficiency of 2.22% were recorded for a polymer:PCBM[70] mixing ratio of 1:4. This is presumably due to the improvement of the morphology of the active layer using o‐DCB as processing solvent. © 2013 Society of Chemical Industry     

Field normalized citation rates, field normalized journal impact and Norwegian weights for allocation of university research funds

We compared three different bibliometric evaluation approaches: two citation-based approaches and one based on manual classification of publishing channels into quality levels. Publication data for two universities was used, and we worked with two levels of analysis: article and department. For the article level, we investigated the predictive power of field normalized citation rates and field normalized journal impact with respect to journal level. The results for the article level show that evaluation of journals based on citation impact correlate rather well with manual classification of journals into quality levels. However, the prediction from field normalized citation rates to journal level was only marginally better than random guessing. At the department level, we studied three different indicators in the context of research fund allocation within universities and the extent to which the three indicators produce different distributions of research funds. It turned out that the three distributions of relative indicator values were very similar, which in turn yields that the corresponding distributions of hypothetical research funds would be very similar.